Details of the Researcher

PHOTO

Hitoshi Shirakawa
Section
Graduate School of Agricultural Science
Job title
Professor
Degree

  • 博士（農学）（東北大学）

  • 農学修士（東北大学）

Committee Memberships 14

  • 公益社団法人 ビタミン・バイオファクター協会　参与

    2025/06 - Present

  • 日本ビタミン学会　理事

    2023/06 - Present

  • 日本栄養・食糧学会　理事・東北支部支部長

    2022/06 - Present

  • 日本無菌生物ノートバイオロジー学会　常任理事

    2019/01 - Present

  • 日本ビタミン学会編集員会　トピックス等担当委員

    2006/05 - 2024/05

  • 日本ビタミン学会　代議員

    2013/11 - 2023/05

  • 日本無菌生物ノートバイオロジー学会　理事

    2018/01 - 2019/01

  • 日本無菌生物ノートバイオロジー学会　評議員

    2006/01 - 2018/01

  • International Association for Gnotobiology　Councillor

    2011/01 - 2017/12

  • 日本ビタミン学会　評議員

    2006/05 - 2013/10

  • 日本農芸化学会　JABEE対応委員

    2003/04 - 2011/03

  • 日本栄養食糧学会　東北支部庶務幹事

    2008/04 - 2010/03

  • 日本農芸化学会　東北支部庶務幹事

    2005/04 - 2007/03

  • 日本無菌生物ノートバイオロジー学会　総会事務

    2005/10 - 2006/01

Show all ︎Show first 5

Professional Memberships 5

  • 日本ビタミン学会

  • 日本無菌生物・ノートバイオロジー学会

  • 日本栄養食糧学会

  • 日本分子生物学会

  • 日本農芸化学会

Research Interests 6

  • 健康寿命

  • rice bran

  • chromatin

  • transcription regulation

  • life style related disease

  • vitamin

Research Areas 2

  • Life sciences / Applied biochemistry /

  • Life sciences / Food sciences /

Awards 3

  1. 学会賞

    2025/05　日本栄養・食糧学会　健康寿命延伸に資する食品成分の新たな機能性に関する基礎研究

  2. 学会賞

    2024/06　日本ビタミン学会　ビタミンKおよび関連イソプレノイドのもつ新たな健康機能性に関する研究

  3. 日本農芸化学会東北支部奨励賞

    2004/08/26　日本農芸化学会東北支部　ヌクレオソーム結合タンパク質による遺伝子発現調節機構の研究

Papers 161

  1. Development of prediction equations for immunoglobulin A, immunoglobulin G, and immunoglobulin M concentrations in mature milk from Holstein cows using milk infrared spectral data

    Yuri Satake, Teppei Katsura, Tao Zhuang, Megumi Urakawa, Yugo Mineshima, Toshimi Baba, Gaku Yoshida, Haruki Kitazawa, Hitoshi Shirakawa, Takehiko Nakamura, Tomonori Nochi, Yoshifumi Sakai, Masahiro Satoh, Satoshi Haga, Hisashi Aso, Yoshinobu Uemoto

    Journal of Dairy Science　2025/07

    DOI： 10.3168/jds.2024-25991 　

  2. Protective Effects of Fish Oil Against Brain Impairment in Rats with Chronic Ethanol-Induced Liver Damage Involving the NRF2 Pathway and Oxidative Stress

    Qian Xiao, Yi-Hsiu Chen, Lu-Chi Fu, Herlin Ajeng Nurrahma, Jing-Huei Lai, Hitoshi Shirakawa, Suh-Ching Yang

    Antioxidants　2025/06/10

    DOI： 10.3390/antiox14060704 　

  3. Glutamine Administration Attenuates Poly(I:C)-Induced Lung Injury by Reducing Neutrophil Infiltration and Activating the TLR-3 Antiviral Pathway

    Li-Han Su, Wen-Chiuan Tsai, Hitoshi Shirakawa, Yu-Ling Tsai, Sung-Ling Yeh, Chiu-Li Yeh

    Nutrients　2025/05/16

    DOI： 10.3390/nu17101700 　

  4. A Comparative Study of Well-Nourished and Malnutrition-Risk Older People Living in Nursing Home: Vitamin D Status and Physical Function Parameters

    Fenthy Marlina Safitri, Yi-Hsiu Chen, Che-Yu Lee, Jiun-Rong Chen, Hitoshi Shirakawa, Hitoshi Shirakawa

    2025/02/26

    DOI： 10.20944/preprints202502.2077.v1 　

  5. Fermented Rice Bran Mitigated the Syndromes of Type 2 Diabetes in KK-Ay Mice Model

    Afifah Zahra Agista, Ami Kato, Tomoko Goto, takuya koseki, Akira Oikawa, Yusuke Ohsaki, Michiko Yamaki, Chiu Li Yeh, Suh Ching Yang, Ardiansyah, Slamet Budijanto, Michio Komai, HITOSHI SHIRAKAWA

    Metabolites　2024/11

    DOI： 10.3390/metabo14110614 　

  6. PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization

    Junya Ito, Toshitaka Nakamura, Takashi Toyama, Deng Chen, Carsten Berndt, Gereon Poschmann, André Santos Dias Mourão, Sebastian Doll, Mirai Suzuki, Weijia Zhang, Jiashuo Zheng, Dietrich Trümbach, Naoya Yamada, Koya Ono, Masana Yazaki, Yasutaka Kawai, Mieko Arisawa, Yusuke Ohsaki, Hitoshi Shirakawa, Adam Wahida, Bettina Proneth, Yoshiro Saito, Kiyotaka Nakagawa, Eikan Mishima, Marcus Conrad

    Molecular Cell　2024/11

    Publisher: Elsevier BV

    DOI： 10.1016/j.molcel.2024.10.028 　

    ISSN： 1097-2765

  7. The Effects of Rice Bran on Neuroinflammation and Gut Microbiota in Ovariectomized Mice Fed a Drink with Fructose

    Yu-Wen Chao, Yu-Tang Tung, Suh-Ching Yang, Hitoshi Shirakawa, Li-Han Su, Pei-Yu Loe, Wan-Chun Chiu

    Nutrients　2024/09/04

    DOI： 10.3390/nu16172980 　

  8. Effects of fish oil on insulin resistance in the brains of rats with alcoholic liver damage

    Zi-Yu Liu, Qian Xiao, Yi-Hsiu Chen, Hitoshi Shirakawa, Jing-Huei Lai, Yung-Hsiao Chiang, Suh-Ching Yang

    Journal of Functional Foods　2024/09

    DOI： 10.1016/j.jff.2024.106369 　

  9. Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness in Both Clinical Diagnosis and Improving Unhealthy Dietary Lifestyles

    Michio Komai, Dan Takeno, Chiharu Fujii, Joe Nakano, Yusuke Ohsaki, HITOSHI SHIRAKAWA

    Nutrients　2024/06

    DOI： 10.3390/nu16121914 　

  10. Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

    Afifah Zahra Agista, Yu-Shan Chien, takuya koseki, Hazuki Nagaoka, Takuto Ohnuma, Yusuke Ohsaki, Chiu Li Yeh, Suh Ching Yang, Ardiansyah, Slamet Budijanto, Michio Komai, HITOSHI SHIRAKAWA

    Metabolites　2024/06

    DOI： 10.3390/metabo14070359 　

  11. In silico and in vivo experiment of soymilk peptide (tetrapeptide - FFYY) for the treatment of hypertension. International-journal Peer-reviewed

    Md Alauddin, Md Ruhul Amin, Muhammad Ali Siddiquee, Kazuyuki Hiwatashi, Atsushi Shimakage, Saori Takahashi, Mamoru Shinbo, Michio Komai, Hitoshi Shirakawa

    Peptides　175　171170-171170　2024/05

    DOI： 10.1016/j.peptides.2024.171170 　

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    Enzyme-Treated Soymilk (ETS) was produced from Commercial Soymilk (CSM) with the treatment of proteinase PROTIN SD-NY10 (Bacillus amyloliquefaciens). Previously, we have isolated novel peptides from ETS but data related to isolated-peptides are scant. In this study, bio-informatics and in vivo analysis of isolated-peptides showed strong binding affinity to the active site of the Angiotensin Converting Enzyme (ACE). Among four peptides, tetrapeptide Phe-Phe-Tyr-Tyr (FFYY) showed strong binding affinity and inhibitory activity to the ACE-enzyme (binding affinity -9.5 Kcal/mol and inhibitory concentration of 1.9 µM respectively) as well as showed less toxicity compared to other peptides. The animal experiment revealed that single oral dose of FFYY (80 µg/kg body weight/day) effectively ameliorates the systolic, diastolic and mean blood pressure in the spontaneously hypertensive rat (SHR) model. Chronic oral administration of FFYY (80 µg/kg body weight/day for 3 weeks) reduced the systolic blood pressure elevation and ACE activity without any adverse side effects on the physiological and biological parameters of SHR. In conclusion, both in silico and in vivo experiments of soymilk-isolated FFYY peptide showed a promising option as a potential alternative for hypertension treatment without adverse side effects on SHR.

  12. Dietary rice bran attenuates hepatic stellate cell activation and liver fibrosis in mice through enhancing antioxidant ability Peer-reviewed

    Fang Yu Hsu, Suh Ching Yang, Fat Moon Suk, Hitoshi Shirakawa, Wan Chun Chiu, Yi Jen Liao

    Journal of Nutritional Biochemistry　125　2024/03

    DOI： 10.1016/j.jnutbio.2023.109565 　

    ISSN： 0955-2863

    eISSN： 1873-4847

  13. Fermented rice bran supplementation attenuates colonic injury through modulating intestinal aryl hydrocarbon receptor and innate lymphoid cells in mice with dextran sodium sulfate-induced acute colitis Peer-reviewed

    Vi Vi Tang Kang Wee, Hitoshi Shirakawa, Sung Ling Yeh, Chiu Li Yeh

    Journal of Nutritional Biochemistry　123　2024/01

    DOI： 10.1016/j.jnutbio.2023.109493 　

    ISSN： 0955-2863

    eISSN： 1873-4847

  14. Eating Habits and Mental Health of College Students in Japan during the COVID-19 Pandemic Peer-reviewed

    Tomoko Imoto, Yuichiro Hoshino, Yoshiyuki Sato, Yusuke Ohsaki, Hitoshi Shirakawa

    COVID　2023/11/26

    DOI： 10.3390/covid3120119 　

    ISSN： 2673-8112

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    <jats:p>While the relationship between eating habits and mental health has been widely studied, there is limited research focusing on college students during emergency situations such as pandemics. We conducted an online questionnaire survey to address this gap. Clustering analysis was applied to identify students’ eating habits, which are possibly more complex than traditional eating habits. Based on the identified eating habits, the students were separated into five groups. We evaluated the relationship between eating habits and mental health in these five groups using University Personality Inventory scores. Based on the results, the largest group—corresponding to slightly less than half of the participants—had the highest vegetable intake and mental health levels. This aligns with findings from numerous prior studies. However, our novel discovery was the presence of another group within those with higher vegetable intake, who had lower levels of mental health. Conversely, a group with lower vegetable intake had higher levels of mental health; remarkably, students in this group frequently consumed soft drinks, suggesting that, during the COVID-19 emergency, indulgent food and drinks may have played a role in enhancing mental health.</jats:p>

  15. Analysis of Genetic Polymorphism of Bitter Taste Receptor TAS2R38 and TAS2R46, and Its Relationship with Eating and Drinking Habits in Japanese ToMMo Subjects Peer-reviewed

    Michiko YAMAKI, Hiroki SAITO, Takahiro MIMORI, Yoichi SUZUKI, Masao NAGASAKI, Kichiya SUZUKI, Shizuko SATOH-KURIWADA, Noriaki SHOJI, Kunio ISONO, Tomoko GOTO, Hitoshi SHIRAKAWA, Michio KOMAI

    Journal of Nutritional Science and Vitaminology　2023/10/31

    DOI： 10.3177/jnsv.69.347 　

    ISSN： 0301-4800 1881-7742

  16. Genetic aspects of immunoglobulins and cyclophilin A in milk as potential indicators of mastitis resistance in Holstein cows Peer-reviewed

    Yoshinobu Uemoto, Teppei Katsura, Yuma Endo, Koutaro Tanaka, Tao Zhuang, Megumi Urakawa, Toshimi Baba, Gaku Yoshida, Haifei Wang, Haruki Kitazawa, Hitoshi Shirakawa, Takehiko Nakamura, Tomonori Nochi, Hisashi Aso

    Journal of Dairy Science　2023/10

    Publisher: American Dairy Science Association

    DOI： 10.3168/jds.2022-23075 　

    ISSN： 0022-0302

  17. Protective Effects of Gnetin C from Melinjo Seed Extract against High-Fat Diet-Induced Hepatic Steatosis and Liver Fibrosis in NAFLD Mice Model Peer-reviewed

    Tohfa Kabir, Haruki Yoshiba, Afifah Zahra Agista, Halima Sultana, Yusuke Ohsaki, Chiu-Li Yeh, Ryota Hirakawa, Hiroko Tani, Tomoki Ikuta, Tomonori Nochi, Suh-Ching Yang, Hitoshi Shirakawa

    Nutrients　15　(18)　3888-3888　2023/09/06

    Publisher: MDPI AG

    DOI： 10.3390/nu15183888 　

    eISSN： 2072-6643

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    Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, can progress to hepatic steatosis, inflammation, and advanced fibrosis, increasing the risk of cirrhosis. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, is beneficial in treating multiple metabolic diseases. Gnetin C, a resveratrol derivative obtained from Melinjo seed extract (MSE), shares similar health-promoting properties. We investigated the role of gnetin C in preventing NAFLD in a mouse model and compared it with resveratrol. Male C57BL/6J mice were fed a control diet (10% calories from fat), a high-fat choline-deficient (HFCD) diet (46% calories from fat) and HFCD diet supplemented with gnetin C (150 mg/kg BW·day−1) or resveratrol (150 mg/kg BW·day−1) for 12 weeks. Gnetin C supplementation reduced body and liver weight, and improved blood glucose levels and insulin sensitivity. Both gnetin C- and resveratrol reduced hepatic steatosis, with gnetin C also decreasing liver lipid content. Gnetin C and resveratrol ameliorated HFCD diet-induced hepatic fibrosis. The mRNA expression results, and western blot analyses showed that gnetin C and, to some extent, resveratrol downregulated fibrosis markers in the TGF-β1 signaling pathway, indicating a possible safeguarding mechanism against NAFLD. These results suggest that gnetin C supplementation may protect against lipid deposition and hepatic fibrosis.

  18. Dietary supplementation of black rice bran to colon carcinogen-induced mice: Examining the development of colorectal cancer by improving environmental colon conditions Peer-reviewed

    Slamet Budijanto, Winda Nurtiana, Amirotul Muniroh, Yeni Kurniati, Lilis Nuraida, Bambang Pontjo Priosoeryanto, Fitriya Nur Annisa Dewi, Ardiansyah Ardiansyah, Nancy Dewi Yuliana, Safrida Safrida, Hitoshi Shirakawa

    Heliyon　9　(8)　2023/08

    DOI： 10.1016/j.heliyon.2023.e18528 　

    ISSN： 2405-8440

  19. Rice Bran Supplementation Ameliorates Gut Dysbiosis and Muscle Atrophy in Ovariectomized Mice Fed with a High-Fat Diet Peer-reviewed

    Pei Xin Huang, Chiu Li Yeh, Suh Ching Yang, Hitoshi Shirakawa, Chao Lin Chang, Li Hsin Chen, Yen Shuo Chiu, Wan Chun Chiu

    Nutrients　15　(16)　2023/08

    DOI： 10.3390/nu15163514 　

    eISSN： 2072-6643

  20. Fermented Rice Bran Supplementation Inhibits LPS-Induced Osteoclast Formation and Bone Resorption in Mice. International-journal Peer-reviewed

    Takahiro Noguchi, Hideki Kitaura, Aseel Marahleh, Afifah Zahra Agista, Yusuke Ohsaki, Hitoshi Shirakawa, Itaru Mizoguchi

    Nutrients　15　(13)　2023/07/05

    DOI： 10.3390/nu15133044 　

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    Fermented rice bran (FRB) is known to have numerous beneficial bioactivities, amongst which is its anti-inflammatory properties when used as a supplement. To determine its effects, we examined osteoclastogenesis and bone resorption caused by injections of lipopolysaccharide (LPS), using mice with and without FRB supplementation. The results were favorable: those that received FRB showed reduced osteoclast numbers and bone resorption compared to those with the control diet. Notably, receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were shown to be lower in the LPS-treated animals with FRB supplementation. FRB's inhibitory effect on RANKL- and TNF-α-induced osteoclastogenesis was further confirmed in vitro. In culture, macrophages exhibited decreased TNF-α mRNA levels when treated with FRB extract and LPS versus treatment with LPS alone, but there was no significant change in RANKL levels in osteoblasts. We can conclude that FRB supplementation dampens the effect of LPS-induced osteoclastogenesis and bone resorption by controlling TNF-α expression in macrophages and the direct inhibition of osteoclast formation.

  21. Potential Benefits of Epidermal Growth Factor for Inhibiting Muscle Degrative Markers in Rats with Alcoholic Liver Damage Peer-reviewed

    Qian Xiao, Yi Hsiu Chen, Ya Ling Chen, Yu Shan Chien, Li Hsuan Hsieh, Hitoshi Shirakawa, Suh Ching Yang

    International Journal of Molecular Sciences　24　(10)　2023/05

    DOI： 10.3390/ijms24108845 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  22. Effects of household-scale cooking on volatile compounds, sensory profile, and hypotensive effect of Kenikir (Cosmos caudatus) Peer-reviewed

    Dody Dwi Handoko, Anisa Maharani Kaseh, Laras Cempaka, Wahyudi David, Bram Kusbiantoro, Afifah Zahra Agista, Yusuke Ohsaki, Hitoshi Shirakawa, Ardiansyah

    AIMS Agriculture and Food　8　(1)　198-213　2023

    DOI： 10.3934/AGRFOOD.2023011 　

    eISSN： 2471-2086

  23. Modification of the oxygen radical absorbance capacity assay and its application in evaluating the total antioxidative state in fish Peer-reviewed

    Toshiki Nakano, Satoshi Hayashi, Yoshihiro Ochiai, Hitoshi Shirakawa, Haiyun Wu, Hideaki Endo, Hui Yu

    Advances in Redox Research　6　100049-100049　2022/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.arres.2022.100049 　

    ISSN： 2667-1379

  24. Biotin Enhances Testosterone Production in Mice and Their Testis-Derived Cells

    Kota Shiozawa, Misato Maeda, Hsin-Jung Ho, Tomoko Katsurai, Md. Zakir Hossain Howlader, Kimiko Horiuchi, Yumi Sugita, Yusuke Ohsaki, Afifah Zahra Agista, Tomoko Goto, Michio Komai, Hitoshi Shirakawa

    Nutrients　14　(22)　4761-4761　2022/11/10

    Publisher: MDPI AG

    DOI： 10.3390/nu14224761 　

    eISSN： 2072-6643

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    Late-onset hypogonadism, a male age-related syndrome characterized by a decline in testosterone production in the testes, is commonly treated with testosterone replacement therapy, which has adverse side effects. Therefore, an alternative treatment is highly sought. Supplementation of a high dosage of biotin, a water-soluble vitamin that functions as a coenzyme for carboxylases involved in carbohydrate, lipid, and amino acid metabolism, has been shown to influence testis functions. However, the involvement of biotin in testis steroidogenesis has not been well clarified. In this study, we examined the effect of biotin on testosterone levels in mice and testis-derived cells. In mice, intraperitoneal treatment with biotin (1.5 mg/kg body weight) enhanced testosterone levels in the serum and testes, without elevating serum levels of pituitary luteinizing hormone. To investigate the mechanism in which biotin increased the testosterone level, mice testis-derived I-10 cells were used. The cells treated with biotin increased testosterone production in a dose- and time-dependent manner. Biotin treatment elevated intracellular cyclic adenosine monophosphate levels via adenylate cyclase activation, followed by the activation of protein kinase A and testosterone production. These results suggest that biotin may have the potential to improve age-related male syndromes associated with declining testosterone production.

  25. Tryptamine, a Microbial Metabolite in Fermented Rice Bran Suppressed Lipopolysaccharide-Induced Inflammation in a Murine Macrophage Model. International-journal

    Afifah Zahra Agista, Sharon Angela Tanuseputero, Takuya Koseki, Ardiansyah, Slamet Budijanto, Halima Sultana, Yusuke Ohsaki, Chiu-Li Yeh, Suh-Ching Yang, Michio Komai, Hitoshi Shirakawa

    International journal of molecular sciences　23　(19)　2022/09/23

    DOI： 10.3390/ijms231911209 　

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    Fermentation is thought to alter the composition and bioavailability of bioactive compounds in rice bran. However, how this process affects the anti-inflammatory effects of rice bran and the bioactive compounds that might participate in this function is yet to be elucidated. This study aimed to isolate bioactive compounds in fermented rice bran that play a key role in its anti-inflammatory function. The fermented rice bran was fractionated using a succession of solvent and solid-phase extractions. The fermented rice bran fractions were then applied to lipopolysaccharide (LPS)-activated murine macrophages to evaluate their anti-inflammatory activity. The hot water fractions (FRBA), 50% ethanol fractions (FRBB), and n-hexane fractions (FRBC) were all shown to be able to suppress the pro-inflammatory cytokine expression from LPS-stimulated RAW 264.7 cells. Subsequent fractions from the hot water fraction (FRBF and FRBE) were also able to reduce the inflammatory response of these cells to LPS. Further investigation revealed that tryptamine, a bacterial metabolite of tryptophan, was abundantly present in these extracts. These results indicate that tryptamine may play an important role in the anti-inflammatory effects of fermented rice bran. Furthermore, the anti-inflammatory effects of FRBE and tryptamine may depend on the activity of the aryl hydrocarbon receptor.

  26. 味覚障害患者における亜鉛に関連した生化学指標の解析

    駒井 三千夫, 川又 美南, 長谷川 雄大, 鈴木 綾, 佐藤 しづ子, 庄司 憲明, 島崎 伸子, 八巻 美智子, 大崎 雄介, 白川 仁

    Biomedical Research on Trace Elements　33　(1)　147-147　2022/09

    Publisher: (一社)日本微量元素学会

    ISSN： 0916-717X

    eISSN： 1880-1404

  27. 【老化と栄養 老化制御と長寿をめぐる医療最前線】糖尿病と高血圧に対して期待されるビオチンの効果

    大崎 雄介, 塩沢 浩太, 白川 仁

    食と医療　22　065-070　2022/08

    Publisher: (株)講談社エディトリアル

  28. The Volatile Compounds and Aroma Profile of Some Pigmented Rice Brans After Fermentation

    Amalia Mar’atun Nadhifah, Dwi Larasatie Nur Fibri, Dody Dwi Handoko, Wahyudi David, Slamet Budijanto, Hitoshi Shirakawa, Ardiansyah Ardiansyah

    Current Research in Nutrition and Food Science Journal　2022/04/29

    DOI： 10.12944/CRNFSJ.10.1.11 　

  29. The Volatile Compounds and Aroma Description in Various Rhizopus oligosporus Solid-State Fermented and Nonfermented Rice Bran

    Retno Dwi Astuti, Dwi Larasatie Nur Fibri, Dody Dwi Handoko, Wahyudi David, Slamet Budijanto, Hitoshi Shirakawa, Ardiansyah Ardiansyah

    Fermentation　2022/03/10

    DOI： 10.3390/fermentation8030120 　

  30. Effects of the Water Extract of Fermented Rice Bran on Liver Damage and Intestinal Injury in Aged Rats with High-Fat Diet Feeding Peer-reviewed

    Ting Yu Chen, Ya Ling Chen, Wan Chun Chiu, Chiu Li Yeh, Yu Tang Tung, Hitoshi Shirakawa, Wei Tzu Liao, Suh Ching Yang

    Plants　11　(5)　607　2022/02

    DOI： 10.3390/plants11050607 　

    eISSN： 2223-7747

  31. Emergence of Novel Functions of Vitamins for the Prevention of Life-Style Related Diseases.

    Kota Shiozawa, Afifah Zahra Agista, Yusuke Ohsaki, Hitoshi Shirakawa

    Journal of nutritional science and vitaminology　68　(Supplement)　S8-S10　2022

    DOI： 10.3177/jnsv.68.S8 　

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    Vitamins are a family of micronutrients comprising 13 groups of organic compounds, of which vitamin B1 was identified first, approximately 110 y ago. Deficiency of each vitamin results in specific symptoms, such as neuropathy, dermatitis, diarrhea, dementia, pernicious anemia, scurvy, blindness, rickets, and bleeding. Almost all vitamins can modulate the functions of enzymes and/or other proteins involved in the formation of bone and soft tissues, generation of energy, and regulation of homeostasis via specific vitamin-protein interactions. In addition to the well-known physiological roles of vitamins, novel modes of action of vitamins have been elucidated. These new functions could contribute to extending healthy life expectancy by preventing and curing lifestyle-related diseases. In this mini-review, we introduce the functional properties of three vitamins, vitamin B3 (niacin), biotin, and vitamin K, for the prevention of age-related diseases.

  32. Prevention of mastitis in multiparous dairy cows with a previous history of mastitis by oral feeding with probiotic <scp> Bacillus subtilis </scp>

    Megumi Urakawa, Tao Zhuang, Hidetoshi Sato, Satoru Takanashi, Kozue Yoshimura, Yuma Endo, Teppei Katsura, Tsuyoshi Umino, Koutaro Tanaka, Hitoshi Watanabe, Hiroko Kobayashi, Naokazu Takada, Tomoyuki Kozutsumi, Hiroaki Kumagai, Takafumi Asano, Kohko Sazawa, Nobuhisa Ashida, Guoqi Zhao, Michael T. Rose, Haruki Kitazawa, Hitoshi Shirakawa, Kouichi Watanabe, Tomonori Nochi, Takehiko Nakamura, Hisashi Aso

    Animal Science Journal　93　(1)　2022/01

    Publisher: Wiley

    DOI： 10.1111/asj.13764 　

    ISSN： 1344-3941

    eISSN： 1740-0929

  33. Effects of dietary vitamin K<inf>3</inf> supplementation on vitamin K<inf>1</inf> and K<inf>2</inf> (menaquinone) dynamics in dairy cows Peer-reviewed

    Hanako Bai, Hikoji Arai, Kentarou Ikuta, Sho Ishikawa, Yoshihisa Ohtani, Kunihiro Iwashita, Nao Okada, Hitoshi Shirakawa, Michio Komai, Fuminori Terada, Yoshiaki Obara

    Animal science journal = Nihon chikusan Gakkaiho　93　(1)　e13680　2022/01/01

    DOI： 10.1111/asj.13680 　

    eISSN： 1740-0929

  34. Effect of vitamin K3 supplementation on immunoglobulin G concentration in colostrum of periparturient Holstein dairy cows Peer-reviewed

    Tomoko Kuroiwa, Yoshihisa Ohtani, Yoshiaki Obara, Fuminori Terada, Kimika Watanabe, Hitoshi Shirakawa, Michio Komai, Hiroshi Satoh, Shigeru Sato, Toshihiro Ichijo

    Animal science journal = Nihon chikusan Gakkaiho　93　(1)　e13706　2022/01/01

    DOI： 10.1111/asj.13706 　

    eISSN： 1740-0929

  35. Fermented rice bran supplementation attenuates chronic colitis-associated extraintestinal manifestations in female C57BL/6N mice Peer-reviewed

    Jahidul Islam, Afifah Zahra Agista, Kouichi Watanabe, Tomonori Nochi, Hisashi Aso, Yusuke Ohsaki, Takuya Koseki, Michio Komai, Hitoshi Shirakawa

    The Journal of Nutritional Biochemistry　99　108855-108855　2022/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.jnutbio.2021.108855 　

    ISSN： 0955-2863

  36. Synbiotics alleviate hepatic damage, intestinal injury and muscular beclin-1 elevation in rats after chronic ethanol administration Peer-reviewed

    Yi Hsiu Chen, Wan Chun Chiu, Qian Xiao, Ya Ling Chen, Hitoshi Shirakawa, Suh Ching Yang

    International Journal of Molecular Sciences　22　(22)　12547　2021/11

    DOI： 10.3390/ijms222212547 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  37. Geranylgeraniol inhibits lipopolysaccharide-induced inflammation in mouse-derived MG6 microglial cells via NF-κB signaling modulation Peer-reviewed

    Wahyu Dwi Saputra, Hiroki Shono, Yusuke Ohsaki, Halima Sultana, Michio Komai, Hitoshi Shirakawa

    International Journal of Molecular Sciences　22　(19)　10543　2021/09

    DOI： 10.3390/ijms221910543 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  38. The prophylactic effects of glutamine on muscle protein synthesis and degradation in rats with ethanol-induced liver damage Peer-reviewed

    Qian Xiao, Yi Hsiu Chen, Satwika Arya Pratama, Ya Ling Chen, Hitoshi Shirakawa, Hsiang Chi Peng, Suh Ching Yang

    Nutrients　13　(8)　2788　2021/08

    DOI： 10.3390/nu13082788 　

    eISSN： 2072-6643

  39. Fermented rice bran supplementation prevents the development of intestinal fibrosis due to dss-induced inflammation in mice Peer-reviewed

    Afifah Zahra Agista, Tubagus Bahtiar Rusbana, Jahidul Islam, Yusuke Ohsaki, Halima Sultana, Ryouta Hirakawa, Kouichi Watanabe, Tomonori Nochi, Ardiansyah, Slamet Budijanto, Suh Ching Yang, Takuya Koseki, Hisashi Aso, Michio Komai, Hitoshi Shirakawa

    Nutrients　13　(6)　1869　2021/06

    DOI： 10.3390/nu13061869 　

    eISSN： 2072-6643

  40. Volatile compounds, sensory profile and phenolic compounds in fermented rice bran Peer-reviewed

    Ardiansyah, Annisa Nada, Nuraini Tiara Indah Rahmawati, Annisa Oktriani, Wahyudi David, Rizki Maryam Astuti, Dody Dwi Handoko, Bram Kusbiantoro, Slamet Budijanto, Hitoshi Shirakawa

    Plants　10　(6)　1073-1073　2021/06

    DOI： 10.3390/plants10061073 　

    eISSN： 2223-7747

  41. Complementary effects of pine bark extract supplementation on inattention, impulsivity, and antioxidative status in children with attention-deficit hyperactivity disorder: A double-blinded randomized placebo-controlled cross-over study Peer-reviewed

    Cheng Dien Hsu, Li Hsuan Hsieh, Ya Ling Chen, I. Cheng Lin, Ying Ru Chen, Chih Chi Chen, Hitoshi Shirakawa, Suh Ching Yang

    Phytotherapy Research　35　(6)　3226-3235　2021/06

    DOI： 10.1002/ptr.7036 　

    ISSN： 0951-418X

    eISSN： 1099-1573

  42. Effect of vitamin K-mediated pxr activation on drug-metabolizing gene expression in human intestinal carcinoma ls180 cell line Peer-reviewed

    Halima Sultana, Ayaka Kato, Ai Ohashi, Rie Takashima, Tomoko Katsurai, Shoko Sato, Masafumi Monma, Yusuke Ohsaki, Tomoko Goto, Michio Komai, Hitoshi Shirakawa

    Nutrients　13　(5)　1709　2021/05

    DOI： 10.3390/nu13051709 　

    eISSN： 2072-6643

  43. S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells Peer-reviewed

    Md Masud Rana, Kota Shiozawa, Katsuyuki Mukai, Katsuhiko Takayanagi, Koichi Eguchi, Halima Sultana, Yusuke Ohsaki, Michio Komai, Hitoshi Shirakawa

    Molecules (Basel, Switzerland)　26　(6)　1697　2021/03/18

    DOI： 10.3390/molecules26061697 　

    eISSN： 1420-3049

  44. In vivo emergence of beige-like fat in chickens as physiological adaptation to cold environments Peer-reviewed

    Rina Sotome, Akira Hirasawa, Motoi Kikusato, Taku Amo, Kyohei Furukawa, Anna Kuriyagawa, Kouichi Watanabe, Anne Collin, Hitoshi Shirakawa, Ryota Hirakawa, Yuta Tanitaka, Hideki Takahashi, Guoyao Wu, Tomonori Nochi, Tsuyoshi Shimmura, Craig H. Warden, Masaaki Toyomizu

    Amino Acids　53　(3)　381-393　2021/03

    DOI： 10.1007/s00726-021-02953-5 　

    ISSN： 0939-4451

    eISSN： 1438-2199

  45. Physiological roles of tryptophan decarboxylase revealed by overexpression of SlTDC1 in tomato Peer-reviewed

    Yui Tsunoda, Shohei Hano, Nozomi Imoto, Tomoki Shibuya, Hiroki Ikeda, Kayoko Amagaya, Kazuhisa Kato, Hitoshi Shirakawa, Hisashi Aso, Yoshinori Kanayama

    Scientia Horticulturae　275　109672　2021/01/03

    DOI： 10.1016/j.scienta.2020.109672 　

    ISSN： 0304-4238

  46. Non-volatile compounds and blood pressure-lowering activity of Inpari 30 and Cempo Ireng fermented and non-fermented rice bran Peer-reviewed

    Ardiansyah, Fauziyyah Ariffa, Rizki Maryam Astuti, Wahyudi David, Dody Dwi Handoko, Slamet Budijanto, Hitoshi Shirakawa

    AIMS Agriculture and Food　6　(1)　337-359　2021/01

    DOI： 10.3934/agrfood.2021021 　

    eISSN： 2471-2086

  47. Impacts of fish oil on the gut microbiota of rats with alcoholic liver damage Peer-reviewed

    Ya Ling Chen, Hitoshi Shirakawa, Nien Shan Lu, Hsiang Chi Peng, Qian Xiao, Suh Ching Yang

    Journal of Nutritional Biochemistry　86　108491　2020/12

    DOI： 10.1016/j.jnutbio.2020.108491 　

    ISSN： 0955-2863

    eISSN： 1873-4847

  48. Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability International-journal Peer-reviewed

    Yusuke Matsuno, Yuko Atsumi, Md Alauddin, Md Masud Rana, Haruka Fujimori, Mai Hyodo, Atsuhiro Shimizu, Tomoki Ikuta, Hiroko Tani, Hidetaka Torigoe, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Michio Komai, Hitoshi Shirakawa, Ken ichi Yoshioka

    Scientific Reports　10　(1)　5388　2020/12/01

    DOI： 10.1038/s41598-020-62292-5 　

    eISSN： 2045-2322

  49. Cysteine sulfoxides enhance steroid hormone production via activation of the protein kinase a pathway in testis-derived I-10 tumor cells Peer-reviewed

    Yuya Nakayama, Hsin Jung Ho, Miki Yamagishi, Hiroyuki Ikemoto, Michio Komai, Hitoshi Shirakawa

    Molecules　25　(20)　4694　2020/10

    DOI： 10.3390/molecules25204694 　

    eISSN： 1420-3049

  50. Supplementation with fermented rice bran attenuates muscle atrophy in a diabetic rat model Peer-reviewed

    Tubagus Bahtiar Rusbana, Afifah Zahra Agista, Wahyu Dwi Saputra, Yusuke Ohsaki, Kouichi Watanabe, Ardy Ardiansyah, Slamet Budijanto, Takuya Koseki, Hisashi Aso, Michio Komai, Hitoshi Shirakawa

    Nutrients　12　(8)　2409　2020/08

    DOI： 10.3390/nu12082409 　

    eISSN： 2072-6643

  51. Beneficial effects of vitamin K status on glycemic regulation and diabetes mellitus: A mini-review Peer-reviewed

    Hsin Jung Ho, Michio Komai, Hitoshi Shirakawa

    Nutrients　12　(8)　2485　2020/08

    DOI： 10.3390/nu12082485 　

    eISSN： 2072-6643

  52. Fish oil up-regulates hepatic autophagy in rats with chronic ethanol consumption International-journal International-coauthorship Peer-reviewed

    Nien Shan Lu, Wan Chun Chiu, Ya Ling Chen, Hsiang Chi Peng, Hitoshi Shirakawa, Suh Ching Yang

    Journal of Nutritional Biochemistry　77　108314　2020/03

    DOI： 10.1016/j.jnutbio.2019.108314 　

    ISSN： 0955-2863

    eISSN： 1873-4847

  53. The effect of liver hydrolysate on chronic ethanol-induced hepatic injury in normal rats International-journal Peer-reviewed

    Kotaro Yamada, Kazuma Ueda, Hitoshi Shirakawa, Puspo Edi Giriwono, Satoru Honda, Hidetomo Sakurai, Michio Komai

    Biological and Pharmaceutical Bulletin　43　(3)　554-557　2020/03/01

    DOI： 10.1248/bpb.b19-00848 　

    ISSN： 0918-6158

    eISSN： 1347-5215

  54. Fermented rice bran extract improves blood pressure and glucose in stroke-prone spontaneously hypertensive rats International-journal International-coauthorship Peer-reviewed

    Ardiansyah, Wahyudi David, Dody Dwi Handoko, Bram Kusbiantoro, Slamet Budijanto, Hitoshi Shirakawa

    Nutrition and Food Science　49　(5)　844-853　2019/09/09

    DOI： 10.1108/NFS-12-2018-0340 　

    ISSN： 0034-6659

    eISSN： 1758-6917

  55. Rice Bran Reduces Weight Gain and Modulates Lipid Metabolism in Rats with High-Energy-Diet-Induced Obesity. International-journal International-coauthorship Peer-reviewed

    Suh-Ching Yang, Wen-Ching Huang, Xin Er Ng, Mon-Chien Lee, Yi-Ju Hsu, Chi-Chang Huang, Hai-Hsin Wu, Chiu-Li Yeh, Hitoshi Shirakawa, Slamet Budijanto, Te-Hsuan Tung, Yu-Tang Tung

    Nutrients　11　(9)　2033　2019/08/30

    DOI： 10.3390/nu11092033 　

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    Obesity has become an epidemic worldwide. It is a complex metabolic disorder associated with many serious complications and high morbidity. Rice bran is a nutrient-dense by product of the rice milling process. Asia has the world's highest rice production (90% of the world's rice production); therefore, rice bran is inexpensive in Asian countries. Moreover, the high nutritional value of the rice bran suggests its potential as a food supplement promoting health improvements, such as enhancing brain function, lowering blood pressure, and regulating pancreatic secretion. The present study evaluated the anti-obesity effect of rice bran in rats with high-energy diet (HED)-induced obesity. Male Sprague-Dawley rats were randomly divided into one of five diet groups (n = 10 per group) and fed the following for eight weeks: Normal diet with vehicle treatment, HED with vehicle, rice bran-0.5X (RB-0.5X) (2% wt/wt rice bran), RB-1.0X (4% wt/wt rice bran), and RB-2.0X (8% wt/wt rice bran). Rice bran (RB-1.0X and RB-2.0X groups) markedly reduced obesity, including body weight and adipocyte size. In addition, treating rats with HED-induced obesity using rice bran significantly reduced the serum uric acid and glucose as well as the liver triglyceride (TG) and total cholesterol (TC). Furthermore, administration of an HED to obese rats significantly affected hepatic lipid homeostasis by increasing phosphotidylcholine (PC; 18:2/22:6), diacylglycerol (DG; 18:2/16:0), DG (18:2/18:1), DG (18:1/16:0), cholesteryl ester (CE; 20:5), CE (28:2), TG (18:0/16:0/18:3), and glycerol-1-2-hexadecanoate 3-octadecanoate. However, the rice bran treatment demonstrated an anti-adiposity effect by partially reducing the HED-induced DG (18:2/18:1) and TG (18:0/16:0/18:3) increases in obese rats. In conclusion, rice bran could act as an anti-obesity supplement in rats, as demonstrated by partially reducing the HED-induced DG and TG increases in obese rats, and thus limit the metabolic diseases associated with obesity and the accumulation of body fat and hepatic lipids in rats.

  56. Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-κB Signaling Pathway. International-journal Peer-reviewed

    Wahyu Dwi Saputra, Nao Aoyama, Michio Komai, Hitoshi Shirakawa

    International journal of molecular sciences　20　(9)　2317　2019/05/10

    DOI： 10.3390/ijms20092317 　

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    The overactivation of microglia is known to trigger inflammatory reactions in the central nervous system, which ultimately induce neuroinflammatory disorders including Alzheimer's disease. However, increasing evidence has shown that menaquinone-4 (MK-4), a subtype of vitamin K2, can attenuate inflammation in the peripheral system. Whereas it was also observed at high levels within the brain, its function in this organ has not been well characterized. Therefore, we investigated the effect of MK-4 on microglial activation and clarified the underlying mechanism. Mouse microglia-derived MG6 cells were exposed to lipopolysaccharide (LPS) either with or without MK-4 pretreatment. Cell responses with respect to inflammatory cytokines (Il-1β, Tnf-α, and Il-6) were measured by qRT-PCR. We further analyzed the phosphorylation of TAK1, IKKα/β, and p65 of the NF-κB subunit by Western blotting. We observed that in LPS-induced MG6 cells, MK-4 dose-dependently suppressed the upregulation of inflammatory cytokines at the mRNA level. It also significantly decreased the phosphorylation of p65, but did not affect that TAK1 and IKKα/β. Furthermore, the nuclear translocation of NF-κB in LPS-induced MG6 cells was inhibited by MK-4. These results indicate that MK-4 attenuates microglial inflammation by inhibiting NF-κB signaling.

  57. Geranylgeraniol Suppresses the Expression of IRAK1 and TRAF6 to Inhibit NFκB Activation in Lipopolysaccharide-Induced Inflammatory Responses in Human Macrophage-Like Cells. International-journal Peer-reviewed

    Puspo E Giriwono, Hitoshi Shirakawa, Yusuke Ohsaki, Shoko Sato, Yukihide Aoyama, Hsin-Jung Ho, Tomoko Goto, Michio Komai

    International journal of molecular sciences　20　(9)　2320　2019/05/10

    DOI： 10.3390/ijms20092320 　

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    Geranylgeraniol (GGOH), a natural isoprenoid found in plants, has anti-inflammatory effects via inhibiting the activation of nuclear factor-kappa B (NFκB). However, its detailed mechanism has not yet been elucidated. Recent studies have revealed that isoprenoids can modulate signaling molecules in innate immune responses. We found that GGOH decreased the expression of lipopolysaccharide (LPS)-induced inflammatory genes in human macrophage-like THP-1 cells. Furthermore, we observed that the suppression of NFκB signaling proteins, in particular interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), occurred in GGOH-treated cells prior to LPS stimulation, suggesting an immunomodulatory effect. These results indicate that GGOH may modulate and help prevent excessive NFκB activation that can lead to numerous diseases.

  58. Rat-derived feeder cells immortalized by expression of mutant CDK4, cyclin D, and telomerase can support stem cell growth. International-journal Peer-reviewed

    Masafumi Katayama, Tohru Kiyono, Kengo Kuroda, Kazuma Ueda, Manabu Onuma, Hitoshi Shirakawa, Tomokazu Fukuda

    Biochimica et biophysica acta. Molecular cell research　1866　(5)　945-956　2019/05

    DOI： 10.1016/j.bbamcr.2019.02.013 　

    ISSN： 0167-4889

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    The maintenance of stem cells often requires the support of feeder cells. Primary mouse embryonic fibroblasts (MEFs) have traditionally been used as feeder cells, and although these MEF-derived feeder cells have exhibited a reasonable performance, they require repeated cell isolation, since MEFs cannot expand indefinitely. To overcome this limitation, immortalized cells, such as STO cells, have been used. However, one major disadvantage is that previously reported immortalized cells can only support stem cell cultures for a relatively short period, typically 4 to 7 days. In this study, we found that our newly established rat-derived fibroblasts immortalized by the expression of mutant cyclin-dependent kinase 4, cyclin D, and telomerase reverse transcriptase, can function as feeder cells for relatively long cell culture periods of approximately 14 days. The rat-derived immortalized cells developed in this study should be a useful source of feeder cells to support stem cell research.

  59. Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells. International-journal Peer-reviewed

    Hsin-Jung Ho, Hitoshi Shirakawa, Keisukei Hirahara, Hideyuki Sone, Shin Kamiyama, Michio Komai

    International journal of molecular sciences　20　(8)　1995　2019/04/23

    DOI： 10.3390/ijms20081995 　

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    Vitamin K2 is indispensable for blood coagulation and bone metabolism. Menaquinone-4 (MK-4) is the predominant homolog of vitamin K2, which is present in large amounts in the pancreas, although its function is unclear. Meanwhile, β-cell dysfunction following insulin secretion has been found to decrease in patients with type 2 diabetes mellitus. To elucidate the physiological function of MK-4 in pancreatic β-cells, we studied the effects of MK-4 treatment on isolated mouse pancreatic islets and rat INS-1 cells. Glucose-stimulated insulin secretion significantly increased in isolated islets and INS-1 cells treated with MK-4. It was further clarified that MK-4 enhanced cAMP levels, accompanied by the regulation of the exchange protein directly activated by the cAMP 2 (Epac2)-dependent pathway but not the protein kinase A (PKA)-dependent pathway. A novel function of MK-4 on glucose-stimulated insulin secretion was found, suggesting that MK-4 might act as a potent amplifier of the incretin effect. This study therefore presents a novel potential therapeutic approach for impaired insulinotropic effects.

  60. Metabolome profiling of growth hormone transgenic coho salmon by capillary electrophoresis time-of-flight mass spectrometry

    Toshiki Nakano, Hitoshi Shirakawa, Giles Yeo, Robert H. Devlin, Tomoyoshi Soga

    Oceanography Challenges to Future Earth: Human and Natural Impacts on our Seas　223-234　2019/02/15

    Publisher: Springer International Publishing

    DOI： 10.1007/978-3-030-00138-4_18 　

  61. Emerging roles of nutraceuticals from selected fermented foods in lifestyle-related disease prevention

    Jahidul Islam, Hitoshi Shirakawa, Yearul Kabir

    Herbal Medicine in India: Indigenous Knowledge, Practice, Innovation and its Value　479-488　2019/01/01

    Publisher: Springer Singapore

    DOI： 10.1007/978-981-13-7248-3_29 　

  62. Development of rice bran functional food and evaluation of its healthful properties International-coauthorship Peer-reviewed

    Md Alauddin, Sadia Rahman, Jahidul Islam, Hitoshi Shirakawa, Michio Komai, Md Zakir Hossen Howlader

    Rice Bran and Rice Bran Oil: Chemistry, Processing and Utilization　183-206　2019/01/01

    DOI： 10.1016/B978-0-12-812828-2.00008-1 　

  63. Nutritional composition of the indigenous cultivar of black cumin seeds from Bangladesh International-journal International-coauthorship Peer-reviewed

    Yearul Kabir, Hitoshi Shirakawa, Michio Komai

    Progress in Nutrition　21　428-434　2019

    DOI： 10.23751/pn.v21i1-S.6556 　

    ISSN： 1129-8723

  64. Orexigenic action of oral zinc: Metabolomic analysis in the rat hypothalamus Peer-reviewed

    Nishiuchi, M., Sakai, K., Tajima, H., Katayama, K., Kimura, F., Hoshi, S., Goto, T., Shirakawa, H., Komai, M.

    Bioscience, Biotechnology and Biochemistry　82　(12)　2168-2175　2018/12

    DOI： 10.1080/09168451.2018.1516543 　

    ISSN： 0916-8451

  65. Adenosine and adenosine-5'-monophosphate ingestion ameliorates abnormal glucose metabolism in mice fed a high-fat diet. International-journal International-coauthorship Peer-reviewed

    Ardiansyah, Inagawa Y, Koseki T, Agista AZ, Ikeda I, Goto T, Komai M, Shirakawa H

    BMC complementary and alternative medicine　18　(1)　304　2018/11

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s12906-018-2367-6 　

    eISSN： 1472-6882

  66. Development of novel silanol-based human pregnane X receptor (PXR) agonists with improved receptor selectivity Peer-reviewed

    Toyama, H., Shirakawa, H., Komai, M., Hashimoto, Y., Fujii, S.

    Bioorganic and Medicinal Chemistry　26　(15)　4493-4501　2018/08

    DOI： 10.1016/j.bmc.2018.07.038 　

    ISSN： 0968-0896

  67. Effects of vitamin K<inf>2</inf> on the expression of genes involved in bile acid synthesis and glucose homeostasis in mice with humanized PXR Peer-reviewed

    Sultana, H., Watanabe, K., Rana, M.M., Takashima, R., Ohashi, A., Komai, M., Shirakawa, H.

    Nutrients　10　(8)　982　2018/07

    DOI： 10.3390/nu10080982 　

  68. Intermolecular hydrogen bond stretching vibrations observed in terahertz spectra of crystalline vitamins

    Masae Takahashi, Nobuyuki Okamura, Xiaomeng Ding, Hitoshi Shirakawa, Hiroaki Minamide

    CrystEngComm　20　(14)　1960-1969　2018/04/14

    Publisher: Royal Society of Chemistry

    DOI： 10.1039/c8ce00095f 　

    ISSN： 1466-8033

  69. Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models. International-journal Peer-reviewed

    Takeda TA, Miyazaki S, Kobayashi M, Nishino K, Goto T, Matsunaga M, Ooi M, Shirakawa H, Tani F, Kawamura T, Komai M, Kambe T

    Communications biology　1　113-113　2018

    DOI： 10.1038/s42003-018-0118-3 　

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    Zinc deficiency causes myriad pathophysiological symptoms, but why distinct phenotypes are generated by zinc deficiency remains unclear. Considering that several ectoenzymes involved in purinergic signaling through extracellular adenine-nucleotide hydrolysis possess zinc ions in their active sites, and disorders in purinergic signaling result in diverse diseases that are frequently similar to those caused by zinc deficiency, herein we examine whether zinc deficiency affects extracellular adenine-nucleotide metabolism. Zinc deficiency severely impairs the activities of major ectoenzymes (ENPP1, ENPP3, NT5E/CD73, and TNAP), and also strongly suppresses adenine-nucleotide hydrolysis in cell-membrane preparations or rat plasma, thereby increasing ATP and ADP levels and decreasing adenosine levels. Thus, zinc deficiency delays both extracellular ATP clearance and adenosine generation, and zinc modulates extracellular adenine-nucleotide metabolism. Since the finely tuned balance between extracellular adenine nucleotides and adenosine is critical for purinergic signaling, these findings provide a novel insight into why zinc deficiency results in diverse symptoms.

  70. Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice Peer-reviewed

    Jahidul Islam, Takuya Koseki, Kouichi Watanabe, Ardiansyah, Slamet Budijanto, Akira Oikawa, Md Alauddin, Tomoko Goto, Hisahi Aso, Michio Komai, Hitoshi Shirakawa

    NUTRIENTS　9　(7)　747　2017/07

    DOI： 10.3390/nu9070747 　

    ISSN： 2072-6643

  71. Relationship between serum zinc level and the preference for foods in health subjects. Peer-reviewed

    Nishiuchi M, Tsuchiya T, Kadowaki A, Goto T, Shirakawa H, Komai M

    Biomed. Res. Trace Elem.　27　(4)　162-168　2017/04/11

    Publisher:

    DOI： 10.11299/brte.27.162 　

    ISSN： 0916-717X

  72. Temperature Dependence in the Terahertz Spectrum of Nicotinamide: Anharmonicity and Hydrogen-Bonded Network Peer-reviewed

    Masae Takahashi, Nubuyuki Okamura, Xinyi Fan, Hitoshi Shirakawa, Hiroaki Minamide

    JOURNAL OF PHYSICAL CHEMISTRY A　121　(13)　2558-2564　2017/04

    DOI： 10.1021/acs.jpca.6b11049 　

    ISSN： 1089-5639

  73. Genotyping Analysis of Bitter-Taste Receptor Genes TAS2R38 and TAS2R46 in Japanese Patients with Gastrointestinal Cancers Peer-reviewed

    Michiko Yamaki, Hiroki Saito, Kunio Isono, Tomoko Goto, Hitoshi Shirakawa, Noriaki Shoji, Shizuko Satoh-Kuriwada, Takashi Sasano, Ryo Okada, Katsuyoshi Kudoh, Fuyuhiko Matoi, Michiaki Unno, Michio Komai

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY　63　(2)　148-154　2017/04

    DOI： 10.3177/jnsv.63.148 　

    ISSN： 0301-4800

    eISSN： 1881-7742

  74. Inhibitory effects of Kaempferia parviflora extract on monocyte adhesion and cellular reactive oxygen species production in human umbilical vein endothelial cells Peer-reviewed

    Satoru Horigome, Izumi Yoshida, Shihomi Ito, Shuichi Inohana, Kei Fushimi, Takeshi Nagai, Akihiro Yamaguchi, Kazuhiro Fujita, Toshiya Satoyama, Shin-ichi Katsuda, Shinobu Suzuki, Masatoshi Watai, Naoto Hirose, Takahiro Mitsue, Hitoshi Shirakawa, Michio Komai

    EUROPEAN JOURNAL OF NUTRITION　56　(3)　949-964　2017/04

    DOI： 10.1007/s00394-015-1141-5 　

    ISSN： 1436-6207

    eISSN： 1436-6215

  75. Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice Peer-reviewed

    Jahidul Islam, Shoko Sato, Kouichi Watanabe, Takaya Watanabe, Ardiansyah, Keisuke Hirahara, Yukihide Aoyama, Shuhei Tomita, Hisashi Aso, Michio Komai, Hitoshi Shirakawa

    JOURNAL OF NUTRITIONAL BIOCHEMISTRY　42　43-50　2017/04

    DOI： 10.1016/j.jnutbio.2016.12.019 　

    ISSN： 0955-2863

    eISSN： 1873-4847

  76. Fermented rice bran supplementation mitigates metabolic syndrome in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Md Alauddin, Hitoshi Shirakawa, Takuya Koseki, Naoko Kijima, Ardiansyah, Slamet Budijanto, Jahidul Islam, Tomoko Goto, Michio Komai

    BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE　16　442　2016/11

    DOI： 10.1186/s12906-016-1427-z 　

    ISSN： 1472-6882

  77. Effect of Kaempferia paruiflora extract and its polymethoxyflavonoid components on testosterone production in mouse testis-derived tumour cells Peer-reviewed

    Satoru Horigome, Misato Maeda, Hsin-Jung Ho, Hitoshi Shirakawa, Michio Komai

    JOURNAL OF FUNCTIONAL FOODS　26　529-538　2016/10

    DOI： 10.1016/j.jff.2016.08.008 　

    ISSN： 1756-4646

  78. Measurement of serotonin distribution and 5-hydoxyindoleacetic acid excretion after oral administration of serotonin using HPLC fluorescence detection. Peer-reviewed

    Islam J, Shirakawa H, Aso H, Komai M

    Food Sci. Nutr. Technol.　1　000105　2016/08

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    責任著者

  79. Geranylgeraniol enhances testosterone production via the cAMP/protein kinase A pathway in testis-derived I-10 tumor cells Peer-reviewed

    Hsin-Jung Ho, Hitoshi Shirakawa, Risa Yoshida, Asagi Ito, Misato Maeda, Tomoko Goto, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　80　(4)　791-797　2016/04

    DOI： 10.1080/09168451.2015.1123612 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  80. Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317 Peer-reviewed

    Hirozumi Toyama, Shoko Sato, Hitoshi Shirakawa, Michio Komai, Yuichi Hashimoto, Shinya Fujii

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　26　(7)　1817-1820　2016/04

    DOI： 10.1016/j.bmcl.2016.02.031 　

    ISSN： 0960-894X

    eISSN： 1464-3405

  81. Simultaneous analysis of serotonin, tryptophan and tryptamine levels in common fresh fruits and vegetables in Japan using fluorescence HPLC Peer-reviewed

    Jahidul Islam, Hitoshi Shirakawa, Thomas Kim Nguyen, Hisashi Aso, Michio Komai

    FOOD BIOSCIENCE　13　56-59　2016/03

    DOI： 10.1016/j.fbio.2015.12.006 　

    ISSN： 2212-4292

    eISSN： 2212-4306

  82. Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation Peer-reviewed

    Ayako Hashimoto, Miki Nakagawa, Natsuki Tsujimura, Shiho Miyazaki, Kumiko Kizu, Tomoko Goto, Yusuke Komatsu, Ayu Matsunaga, Hitoshi Shirakawa, Hiroshi Narita, Taiho Kambe, Michio Komai

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY　310　(5)　R459-R468　2016/03

    DOI： 10.1152/ajpregu.00439.2015 　

    ISSN： 0363-6119

    eISSN： 1522-1490

  83. Novel function of vitamin K revealed by germfree rodent studies. Peer-reviewed

    Komai M, Shirakawa H, Ohsaki Y, Minegishi Y, Takumi N, Furukawa Y, Kimura S

    J Germfree Life Gnotobiol.　36　1-11　2016

  84. Zinc deficiency causes to decrease plasma calcium and ionized calcium concentrations prior to an increase in the plasma parathyroid hormone concentration in rats Peer-reviewed

    Goto, T., Shirakawa, H., Komai, M.

    Nano Biomedicine　8　(2)　67-73　2016

    DOI： 10.11344/nano.8.67 　

  85. Serotonin Improves High Fat Diet Induced Obesity in Mice. International-journal Peer-reviewed

    Hitoshi Watanabe, Tatsuya Nakano, Ryo Saito, Daisuke Akasaka, Kazuki Saito, Hideki Ogasawara, Takeshi Minashima, Kohtaro Miyazawa, Takashi Kanaya, Ikuro Takakura, Nao Inoue, Ikuo Ikeda, Xiangning Chen, Masato Miyake, Haruki Kitazawa, Hitoshi Shirakawa, Kan Sato, Kohji Tahara, Yuya Nagasawa, Michael T Rose, Shyuichi Ohwada, Kouichi Watanabe, Hisashi Aso

    PloS one　11　(1)　e0147143　2016

    DOI： 10.1371/journal.pone.0147143 　

    More details Close

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  86. Systematic synthesis and anti-inflammatory activity of omega-carboxylated menaquinone derivatives-Investigations on identified and putative vitamin K-2 metabolites Peer-reviewed

    Shinya Fujii, Akitaka Shimizu, Noriaki Takeda, Kazuki Oguchi, Tomoko Katsurai, Hitoshi Shirakawa, Michio Komai, Hiroyuki Kagechika

    BIOORGANIC & MEDICINAL CHEMISTRY　23　(10)　2344-2352　2015/05

    DOI： 10.1016/j.bmc.2015.03.070 　

    ISSN： 0968-0896

    eISSN： 1464-3391

  87. Processed soymilk effectively ameliorates blood pressure elevation in spontaneously hypertensive rats Peer-reviewed

    Md Alauddin, Hitoshi Shirakawa, Kazuyuki Hiwatashi, Atsushi Shimakage, Saori Takahashi, Mamoru Shinbo, Michio Komai

    JOURNAL OF FUNCTIONAL FOODS　14　126-132　2015/04

    DOI： 10.1016/j.jff.2015.01.029 　

    ISSN： 1756-4646

  88. Fermented barley extract supplementation ameliorates metabolic state in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Puspo E. Giriwono, Kazuki Oguchi, Kazuma Ueda, Hideki Hokazono, Kazuyuki Hiwatashi, Saori Takahashi, Shoko Sato, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　79　(11)　1876-1883　2015

    DOI： 10.1080/09168451.2015.1052772 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  89. Impact of fasting time on hepatic lipid metabolism in nutritional animal studies Peer-reviewed

    Ikuo Ikeda, Kanae Metoki, Takashi Yamahira, Masaki Kato, Nao Inoue, Koji Nagao, Teruyoshi Yanagita, Hitoshi Shirakawa, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　78　(9)　1584-1591　2014/09

    DOI： 10.1080/09168451.2014.923297 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  90. Identification and evaluation of anti-inflammatory compounds from Kaempferia parviflora Peer-reviewed

    Satoru Horigome, Izumi Yoshida, Aiko Tsuda, Teppei Harada, Akihiro Yamaguchi, Kumiko Yamazaki, Shuichi Inohana, Satoshi Isagawa, Nobuyuki Kibune, Toshiya Satoyama, Shin-ichi Katsuda, Shinobu Suzuki, Masatoshi Watai, Naoto Hirose, Takahiro Mitsue, Hitoshi Shirakawa, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　78　(5)　851-860　2014/05

    DOI： 10.1080/09168451.2014.905177 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  91. Deletion of Hypoxia-Inducible Factor-1 alpha in Adipocytes Enhances Glucagon-Like Peptide-1 Secretion and Reduces Adipose Tissue Inflammation Peer-reviewed

    Yoshitaka Kihira, Mariko Miyake, Manami Hirata, Yoji Hoshina, Kana Kato, Hitoshi Shirakawa, Hiroshi Sakaue, Noriko Yamano, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki, Shuhei Tomita

    PLOS ONE　9　(4)　e93856　2014/04

    DOI： 10.1371/journal.pone.0093856 　

    ISSN： 1932-6203

  92. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A Peer-reviewed

    Shoko Sato, Hitoshi Shirakawa, Shuhei Tomita, Masahiro Tohkin, Frank J. Gonzalez, Michio Komai

    TOXICOLOGY AND APPLIED PHARMACOLOGY　273　(1)　90-99　2013/11

    DOI： 10.1016/j.taap.2013.08.017 　

    ISSN： 0041-008X

    eISSN： 1096-0333

  93. Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-kappa B activation in rats Peer-reviewed

    Puspo E. Giriwono, Hitoshi Shirakawa, Yusuke Ohsaki, Shuichi Hata, Hiroki Kuriyama, Shoko Sato, Tomoko Goto, Michio Komai

    EUROPEAN JOURNAL OF NUTRITION　52　(3)　1191-1199　2013/04

    DOI： 10.1007/s00394-012-0429-y 　

    ISSN： 1436-6207

  94. Physiological Effects and Tissue Distribution, from Large Doses of Tocotrienol in Rats Peer-reviewed

    Akira Shibata, Kiyotaka Nakagawa, Hitoshi Shirakawa, Teiko Kobayashi, Yuki Kawakami, Rie Takashima, Ai Ohashi, Shoko Sato, Yusuke Ohsaki, Fumiko Kimura, Toshiyuki Kimura, Tsuyoshi Tsuduki, Michio Komai, Teruo Miyazawa

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　76　(9)　1805-1808　2012/09

    DOI： 10.1271/bbb.120387 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  95. Behavioral Analysis of Drosophila Transformants Expressing Human Taste Receptor Genes in the Gustatory Receptor Neurons Peer-reviewed

    Ryota Adachi, Yuko Sasaki, Hiromi Morita, Michio Komai, Hitoshi Shirakawa, Tomoko Goto, Akira Furuyama, Kunio Isono

    JOURNAL OF NEUROGENETICS　26　(2)　198-205　2012/06

    DOI： 10.3109/01677063.2012.690254 　

    ISSN： 0167-7063

  96. Administration of biotin prevents the development of insulin resistance in the skeletal muscles of Otsuka Long-Evans Tokushima fatty rats Peer-reviewed

    Yuka Sasaki, Hideyuki Sone, Shin Kamiyama, Muneshige Shimizu, Hitoshi Shirakawa, Yasuo Kagawa, Michio Komai, Yuji Furukawa

    FOOD & FUNCTION　3　(4)　414-419　2012/04

    DOI： 10.1039/c2fo10175k 　

    ISSN： 2042-6496

  97. Lupeol Supplementation Improves Blood Pressure and Lipid Metabolism Parameters in Stroke-Prone Spontaneously Hypertensive Rats Peer-reviewed

    Ardiansyah, Eri Yamaguchi, Hitoshi Shirakawa, Keishi Hata, Kazuyuki Hiwatashi, Kousaku Ohinata, Tomoko Goto, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　76　(1)　183-185　2012/01

    DOI： 10.1271/bbb.110559 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  98. Novel Effect of Adenosine 5 '-Monophosphate on Ameliorating Hypertension and the Metabolism of Lipids and Glucose in Stroke-Prone Spontaneously Hypertensive Rats Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Kazuyuki Hiwatashi, Saori Takahasi, Yoshinobu Akiyama, Michio Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　59　(24)　13238-13245　2011/12

    DOI： 10.1021/jf203237c 　

    ISSN： 0021-8561

  99. Fermented Barley Extract Supplementation Maintained Antioxidative Defense Suppressing Lipopolysaccharide-Induced Inflammatory Liver Injury in Rats Peer-reviewed

    Puspo E. Giriwono, Hitoshi Shirakawa, Hideki Hokazono, Tomoko Goto, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　75　(10)　1971-1976　2011/10

    DOI： 10.1271/bbb.110374 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  100. Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells Peer-reviewed

    Asagi Ito, Hitoshi Shirakawa, Naofumi Takumi, Yoshihiko Minegishi, Ai Ohashi, Zakir H. Howlader, Yusuke Ohsaki, Toshiro Sato, Tomoko Goto, Michio Komai

    LIPIDS IN HEALTH AND DISEASE　10　158　2011/09

    DOI： 10.1186/1476-511X-10-158 　

    ISSN： 1476-511X

  101. Dietary vitamin K alleviates the reduction in testosterone production induced by lipopolysaccharide administration in rat testis Peer-reviewed

    Naofumi Takumi, Hitoshi Shirakawa, Yusuke Ohsaki, Asagi Ito, Takaya Watanabe, Puspo E. Giriwono, Toshiro Sato, Michio Komai

    FOOD & FUNCTION　2　(7)　406-411　2011/07

    DOI： 10.1039/c1fo10058k 　

    ISSN： 2042-6496

  102. Regulation of blood pressure and glucose metabolism induced by L-tryptophan in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Yuto Inagawa, Takuya Koseki, Michio Komai

    NUTRITION & METABOLISM　8　45　2011/06

    DOI： 10.1186/1743-7075-8-45 　

    ISSN： 1743-7075

  103. Purification and identification of ACE inhibitory substance from protease-treated Hikiwari-natto and anti-hypertensive effect of Natto on spontaneously hypertensive rats Peer-reviewed

    嶋影逸, 新保守, 山田清繁, Ardiansyah, 白川仁, 駒井三千夫, 樋渡一之, 戸松誠, 高橋砂織

    食品・臨床栄養　e2011_1-8　(1)　1-8　2011

    Publisher: Japan Science Society of Biological Macromolecules

    DOI： 10.11473/fcn.6.1 　

    ISSN： 2187-3259

    More details Close

    <tt>Anti-hypertensive effect has been known as one of the functionalities of natto. It is deduced that natto shows anti-hypertensive effect by inhibiting angiotensin-converting enzyme (ACE), the key enzyme of renin-angiotensin system. Some research results about anti-hypertensive effect of natto have been reported so far, but there are almost no findings about ACE inhibitory substance derived from natto. We purified and identified the substances from protease-treated hikiwari-natto, whoese ACE inhibitory activity was about 1.4 times higher than that of protease-untreated hikiwari-natto. As a result, it was found that ACE inhibitory substances included novel ACE inhibitory peptides such as Ile-Ile, Ile-Asp, Ile-Phe-Tyr, Leu-Phe-Tyr and Leu-Tyr-Tyr. In addition, the extracts of protease-treated hikiwari-natto showed significant reduction in systolic blood pressure when they were orally administered to stroke prone spontaneously hypertensive rats in a single dose (80mg/kg of rat weight)</tt><tt>. </tt>

  104. Daily expression patterns of growth-related genes in growth hormone-transgenic coho salmon, Oncorhynchus kisutch Peer-reviewed

    Nakano T, Shoji Y, Shirakawa H, Suda Y, Yamaguchi T, Sato M, Devlin RH

    La mer　49　(3)　111-116　2011

    Publisher:

    ISSN： 0503-1540

  105. Reduction of Blood Pressure by Soybean Saponins, Renin Inhibitors from Soybean, in Spontaneously Hypertensive Rats Peer-reviewed

    Kazuyuki Hiwatashi, Hitoshi Shirakawa, Kazuyuki Hori, Yumiko Yoshiki, Nao Suzuki, Mika Hokari, Michio Komai, Saori Takahashi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　74　(11)　2310-2312　2010/11

    DOI： 10.1271/bbb.100328 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  106. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor kappa B through the repression of IKK alpha/beta. phosphorylation Peer-reviewed

    Yusuke Ohsaki, Hitoshi Shirakawa, Akihito Miura, Puspo E. Giriwono, Shoko Sato, Ai Ohashi, Maiko Iribe, Tomoko Goto, Michio Komai

    JOURNAL OF NUTRITIONAL BIOCHEMISTRY　21　(11)　1120-1126　2010/11

    DOI： 10.1016/j.jnutbio.2009.09.011 　

    ISSN： 0955-2863

  107. Anti-metabolic syndrome effects of adenosine ingestion in stroke-prone spontaneously hypertensive rats fed a high-fat diet Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Yumi Sugita, Takuya Koseki, Michio Komai

    BRITISH JOURNAL OF NUTRITION　104　(1)　48-55　2010/07

    DOI： 10.1017/S0007114510000255 　

    ISSN： 0007-1145

    eISSN： 1475-2662

  108. Yamabushitake Mushroom (Hericium erinaceus) Improved Lipid Metabolism in Mice Fed a High-Fat Diet Peer-reviewed

    Kazuyuki Hiwatashi, Yasuyuki Kosaka, Nao Suzuki, Keishi Hata, Toshiyuki Mukaiyama, Kenji Sakamoto, Hitoshi Shirakawa, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　74　(7)　1447-1451　2010/07

    DOI： 10.1271/bbb.100130 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  109. Metabolic characteristics and oxidative damage to skeletal muscle in broiler chickens exposed to chronic heat stress Peer-reviewed

    M. A. K. Azad, M. Kikusato, T. Maekawa, H. Shirakawa, M. Toyomizu

    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY　155　(3)　401-406　2010/03

    DOI： 10.1016/j.cbpa.2009.12.011 　

    ISSN： 1095-6433

    eISSN： 1531-4332

  110. Extract of fermented barley attenuates chronic alcohol induced liver damage by increasing antioxidative activities Peer-reviewed

    Puspo E. Giriwono, Takuya Hashimoto, Yusuke Ohsaki, Hitoshi Shirakawa, Hideki Hokazono, Michio Komai

    FOOD RESEARCH INTERNATIONAL　43　(1)　118-124　2010/01

    DOI： 10.1016/j.foodres.2009.09.008 　

    ISSN： 0963-9969

  111. Absorption and Effectiveness of Orally Administered Low Molecular Weight Collagen Hydrolysate in Rats Peer-reviewed

    Mari Watanabe-Kamiyama, Muneshige Shimizu, Shin Kamiyama, Yasuki Taguchi, Hideyuki Sone, Fumiki Morimatsu, Hitoshi Shirakawa, Yuji Furukawa, Michio Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　58　(2)　835-841　2010/01

    DOI： 10.1021/jf9031487 　

    ISSN： 0021-8561

    eISSN： 1520-5118

  112. The Nucleosomal Binding Protein NSBP1 Is Highly Expressed in the Placenta and Modulates the Expression of Differentiation Markers in Placental Rcho-1 Cells Peer-reviewed

    Hitoshi Shirakawa, Mark Rochman, Takashi Furusawa, Michael R. Kuehn, Satoru Horigome, Keiichi Haketa, Yumi Sugita, Tomoyuki Inada, Michio Komai, Michael Bustin

    JOURNAL OF CELLULAR BIOCHEMISTRY　106　(4)　651-658　2009/03

    DOI： 10.1002/jcb.22046 　

    ISSN： 0730-2312

  113. Orally Administered Zinc Increases Food Intake via Vagal Stimulation in Rats Peer-reviewed

    Kousaku Ohinata, Masami Takemoto, Makoto Kawanago, Shuya Fushimi, Hitoshi Shirakawa, Tomoko Goto, Akihiro Asakawa, Michio Komai

    JOURNAL OF NUTRITION　139　(3)　611-616　2009/03

    DOI： 10.3945/jn.108.096370 　

    ISSN： 0022-3166

  114. Adenosine, an Identified Active Component from the Driselase-Treated Fraction of Rice Bran, Is Effective at Improving Metabolic Syndrome in Stroke-Prone Spontaneously Hypertensive Rats Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Taku Shimeno, Takuya Koseki, Yoshihito Shiono, Tetsuya Murayama, Eiko Hatakeyama, Michio Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　57　(6)　2558-2564　2009/03

    DOI： 10.1021/jf803347c 　

    ISSN： 0021-8561

  115. EFFECT OF ADENOSINE ADMINISTRATION ON IMPROVING METABOLIC SYNDROME-RELATED PARAMETERS IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

    Ardiansyah Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Yoshihito Shiono, Tetsuya Murayama, Michio Komai, Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Yoshihito Shiono, Tetsuya Murayama, Michio Komai

    ANNALS OF NUTRITION AND METABOLISM　55　200-200　2009

    ISSN： 0250-6807

  116. Tocotrienol Inhibits Secretion of Angiogenic Factors from Human Colorectal Adenocarcinoma Cells by Suppressing Hypoxia-Inducible Factor-1 alpha Peer-reviewed

    Akira Shibata, Kiyotaka Nakagawa, Phumon Sookwong, Tsuyoshi Tsuduki, Shuhei Tomita, Hitoshi Shirakawa, Michio Komai, Teruo Miyazawa

    JOURNAL OF NUTRITION　138　(11)　2136-2142　2008/11

    DOI： 10.3945/jn.108.093237 　

    ISSN： 0022-3166

  117. Effect of biotin treatment on hepatic gene expression in streptozotocin-induced diabetic rats Peer-reviewed

    Yumi Sugita, Hitoshi Shirakawa, Ritsuko Sugimoto, Yuji Furukawa, Michio Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　72　(5)　1290-1298　2008/05

    DOI： 10.1271/bbb.70781 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  118. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver Peer-reviewed

    Shoko Sato, Hitoshi Shirakawa, Shuhei Tomita, Yusuke Ohsaki, Keiichi Haketa, Osamu Tooi, Noriaki Santo, Masahiro Tohkin, Yuji Furukawa, Frank J. Gonzalez, Michio Komai

    TOXICOLOGY AND APPLIED PHARMACOLOGY　229　(1)　10-19　2008/05

    DOI： 10.1016/j.taap.2007.12.029 　

    ISSN： 0041-008X

  119. Antihypertensive effect of biotin in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Mari Watanabe-Kamiyama, Shin Kamiyama, Kimiko Horiuchi, Kousaku Ohinata, Hitoshi Shirakawa, Yuji Furukawa, Michio Komai

    BRITISH JOURNAL OF NUTRITION　99　(4)　756-763　2008/04

    DOI： 10.1017/S0007114507841122 　

    ISSN： 0007-1145

  120. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Ardiansyah, Yusuke Ohsaki, Hitoshi Shirakawa, Takuya Koseki, Michlo Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　56　(8)　2825-2830　2008/04

    DOI： 10.1021/jf072896y 　

    ISSN： 0021-8561

  121. Decreased expression of carbonic anhydrase isozyme II, rather than of isozyme VI, in submandibular glands in long-term zinc-deficient rats Peer-reviewed

    Tomoko Goto, Hitoshi Shirakawa, Yuji Furukawa, Michio Komai

    BRITISH JOURNAL OF NUTRITION　99　(2)　248-253　2008/02

    DOI： 10.1017/S0007114507801565 　

    ISSN： 0007-1145

  122. The Driselase-treated fraction of rice bran is a more effective dietary factor to improve hypertension, glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats compared to ferulic acid Peer-reviewed

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Katsumi Hashizume, Michio Komai

    BRITISH JOURNAL OF NUTRITION　97　(1)　67-76　2007/01

    DOI： 10.1017/S000711450721013X 　

    ISSN： 0007-1145

  123. Effects of Japanese torreya (Torreya nucifera) seed oil on the activities and mRNA expression of lipid metabolism-related enzymes in rats Peer-reviewed

    Yasushi Endo, Yuko Osada, Fumiko Kimura, Hitoshi Shirakawa, Kenshiro Fujimoto

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　71　(1)　231-233　2007/01

    DOI： 10.1271/bbb.60350 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  124. Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats. International-journal

    Hitoshi Shirakawa, Yusuke Ohsaki, Yoshihiko Minegishi, Naofumi Takumi, Kousaku Ohinata, Yuji Furukawa, Takeo Mizutani, Michio Komai

    Biochimica et biophysica acta　1760　(10)　1482-8　2006/10

    ISSN： 0006-3002

    More details Close

    Vitamin K (K) is an essential factor for the posttranslational modification of blood coagulation factors as well as proteins in the bone matrix (Gla proteins). It is known that K is not only distributed in the liver and bones but also abundantly distributed in the brain, kidney, and gonadal tissues. However, the role of K in these tissues is not well clarified. In this study, we used DNA microarray and identified the genes whose expression was affected in the testis under the K-deficient (K-def) state. The expression of genes involved in the biosynthesis of cholesterol and steroid hormones was decreased in the K-def group. The mRNA levels of Cyp11a - a rate-limiting enzyme in testosterone synthesis - positively correlated with the menaquinone-4 (MK-4) concentration in the testis. Moreover, as compared to the control (Cont) and K-supplemented (K-sup) groups, the K-def group had decreased testosterone concentrations in the plasma and testis. These results suggested that K is involved in steroid production in the testis through the regulation of Cyp11a.

  125. Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats Peer-reviewed

    Hitoshi Shirakawa, Yusuke Ohsaki, Yoshihiko Minegishi, Naofumi Takumi, Kousaku Ohinata, Yuji Furukawa, Takeo Mizutani, Michio Komai

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS　1760　(10)　1482-1488　2006/10

    DOI： 10.1016/j.bbagen.2006.05.008 　

    ISSN： 0304-4165

  126. Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat Peer-reviewed

    Y Ohsaki, H Shirakawa, K Hiwatashi, Y Furukawa, T Mizutani, M Komai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　70　(4)　926-932　2006/04

    DOI： 10.1271/bbb.70.926 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  127. Newly Clarified Function of Vitamin K. Peer-reviewed

    Komai M, Ohsaki Y, Minegishi Y, Takumi N, Shirakawa H

    Tohoku J. Agr. Res.　57　19-31　2006/03

  128. Rice bran fractions improve blood pressure, lipid profile, and glucose metabolism in stroke-prone spontaneously hypertensive rats Peer-reviewed

    Ardiansyah, H Shirakawa, T Koseki, K Ohinata, K Hashizume, M Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　54　(5)　1914-1920　2006/03

    DOI： 10.1021/jf0525611 　

    ISSN： 0021-8561

  129. Acidic C-tail of HMGB1 is required for its target binding to nucleosome linker DNA and transcription stimulation Peer-reviewed

    T Ueda, H Chou, T Kawase, H Shirakawa, M Yoshida

    BIOCHEMISTRY　43　(30)　9901-9908　2004/08

    DOI： 10.1021/bi0359751 　

    ISSN： 0006-2960

  130. Involvement of HMGB1 and HMGB2 proteins in exogenous DNA integration reaction into the genome of HeLaS3 cells Peer-reviewed

    T Ueda, H Shirakawa, M Yoshida

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH　1593　(1)　77-84　2002/12

    DOI： 10.1016/S0167-4889(02)00332-4 　

    ISSN： 0167-4889

  131. Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and promotes interaction with 14.3.3 proteins Peer-reviewed

    M Prymakowska-Bosak, R Hock, F Catez, JH Lim, Y Birger, H Shirakawa, K Lee, M Bustin

    MOLECULAR AND CELLULAR BIOLOGY　22　(19)　6809-6819　2002/10

    DOI： 10.1128/MCB.22.19.6809-6819.2002 　

    ISSN： 0270-7306

  132. Detoxification of oxidized LDL by transferring its oxidation product(s) to lecithin: Cholesterol acyltransferase Peer-reviewed

    ZH Howlader, S Kamiyama, H Shirakawa, Y Murakami, M Ito, M Komai, K Muramoto, Y Furukawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　291　(4)　758-763　2002/03

    DOI： 10.1006/bbrc.2002.6522 　

    ISSN： 0006-291X

  133. Mitotic phosphorylation prevents the binding of HMGN proteins to chromatin Peer-reviewed

    M Prymakowska-Bosak, T Misteli, JE Herrera, H Shirakawa, Y Birger, S Garfield, M Bustin

    MOLECULAR AND CELLULAR BIOLOGY　21　(15)　5169-5178　2001/08

    DOI： 10.1128/MCB.21.15.5169-5178.2001 　

    ISSN： 0270-7306

  134. HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins Peer-reviewed

    KL West, Y Ito, Y Birger, Y Postnikov, H Shirakawa, M Bustin

    JOURNAL OF BIOLOGICAL CHEMISTRY　276　(28)　25959-25969　2001/07

    DOI： 10.1074/jbc.M101692200 　

    ISSN： 0021-9258

  135. HMG box A in HMG2 protein functions as a mediator of DNA structural alteration together with box B-1 Peer-reviewed

    Y Nakamura, K Yoshioka, H Shirakawa, M Yoshida

    JOURNAL OF BIOCHEMISTRY　129　(4)　643-651　2001/04

    DOI： 10.1093/oxfordjournals.jbchem.a002902 　

    ISSN： 0021-924X

  136. Targeting of high mobility group-14/-17 proteins in chromatin is independent of DNA sequence Peer-reviewed

    H Shirakawa, JE Herrera, M Bustin, Y Postnikov

    JOURNAL OF BIOLOGICAL CHEMISTRY　275　(48)　37937-37944　2000/12

    DOI： 10.1074/jbc.M000989200 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  137. NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression Peer-reviewed

    H Shirakawa, D Landsman, YV Postnikov, M Bustin

    JOURNAL OF BIOLOGICAL CHEMISTRY　275　(9)　6368-6374　2000/03

    DOI： 10.1074/jbc.275.9.6368 　

    ISSN： 0021-9258

  138. Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens Peer-reviewed

    W Ma, S Ozaki, J Sobajima, H Uesugi, M Murakami, M Tanaka, M Kozuki, H Hashimoto, Y Fujita, D Kawabata, F Osakada, H Shirakawa, M Yoshida, M Hayami, K Nakao

    AUTOIMMUNITY　32　(4)　281-291　2000

    ISSN： 0891-6934

  139. High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis Peer-reviewed

    J Sobajima, S Ozaki, H Uesugi, F Osakada, M Inoue, Y Fukuda, H Shirakawa, M Yoshida, A Rokuhara, H Imai, K Kiyosawa, K Nakao

    GUT　44　(6)　867-873　1999/06

    ISSN： 0017-5749

  140. The stabilized structural array of two HMG1/2-boxes endowed by a linker sequence between them is requisite for the effective binding of HMG1 with DNA Peer-reviewed

    K Saito, T Kikuchi, H Shirakawa, M Yoshida

    JOURNAL OF BIOCHEMISTRY　125　(2)　399-405　1999/02

    DOI： 10.1093/oxfordjournals.jbchem.a022300 　

    ISSN： 0021-924X

  141. Differences in DNA recognition and conformational change activity between boxes A and B in HMG2 protein Peer-reviewed

    K Yoshioka, K Saito, T Tanabe, A Yamamoto, Y Ando, Y Nakamura, H Shirakawa, M Yoshida

    BIOCHEMISTRY　38　(2)　589-595　1999/01

    DOI： 10.1021/bi981834l 　

    ISSN： 0006-2960

  142. High mobility group proteins 1 and 2 can function as DNA-binding regulatory components for DNA-dependent protein kinase in vitro Peer-reviewed

    Y Yumoto, H Shirakawa, M Yoshida, A Suwa, F Watanabe, H Teraoka

    JOURNAL OF BIOCHEMISTRY　124　(3)　519-527　1998/09

    ISSN： 0021-924X

  143. Non-histone chromosomal proteins HMG1 and 2 enhance ligation reaction of DNA double-strand breaks Peer-reviewed

    S Nagaki, M Yamamoto, Y Yumoto, H Shirakawa, M Yoshida, H Teraoka

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　246　(1)　137-141　1998/05

    DOI： 10.1006/bbrc.1998.8589 　

    ISSN： 0006-291X

  144. Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and KMG2 in systemic rheumatic diseases Peer-reviewed

    H Uesugi, S Ozaki, J Sobajima, F Osakada, H Shirakawa, M Yoshida, K Nakao

    JOURNAL OF RHEUMATOLOGY　25　(4)　703-709　1998/04

    ISSN： 0315-162X

  145. Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC) Peer-reviewed

    J Sobajima, S Ozaki, H Uesugi, F Osakada, H Shirakawa, M Yoshida, K Nakao

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY　111　(2)　402-407　1998/02

    DOI： 10.1046/j.1365-2249.1998.00491.x 　

    ISSN： 0009-9104

  146. Difference in affinity for DNA between HMG proteins 1 and 2 determined by surface plasmon resonance measurements Peer-reviewed

    A Yamamoto, Y Ando, K Yoshioka, K Saito, T Tanabe, H Shirakawa, M Yoshida

    JOURNAL OF BIOCHEMISTRY　122　(3)　586-594　1997/09

    ISSN： 0021-924X

  147. Nuclear accumulation of HMG2 protein is mediated by basic regions interspaced with a long DNA-binding sequence, and retention within the nucleus requires the acidic carboxyl terminus Peer-reviewed

    H Shirakawa, T Tanigawa, S Sugiyama, M Kobayashi, T Terashima, K Yoshida, T Arai, M Yoshida

    BIOCHEMISTRY　36　(20)　5992-5999　1997/05

    DOI： 10.1021/bi962487n 　

    ISSN： 0006-2960

  148. Cloning and sequencing of the gene encoding the plasma membrane H(+)ATPase from an acidophilic red alga, Cyanidium caldarium Peer-reviewed

    H Ohta, H Shirakawa, K Uchida, M Yoshida, Y Matuo, Enami, I

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS　1319　(1)　9-13　1997/03

    DOI： 10.1016/S0005-2728(97)00007-8 　

    ISSN： 0005-2728

  149. Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: Non-histone chromosomal proteins, HMG1 and HMG2 Peer-reviewed

    J Sobajima, S Ozaki, F Osakada, H Uesugi, H Shirakawa, M Yoshida, K Nakao

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY　107　(1)　135-140　1997/01

    ISSN： 0009-9104

  150. Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: Non-histone chromosomal proteins, HMG1 and HMG2 Peer-reviewed

    J Sobajima, S Ozaki, F Osakada, H Uesugi, H Shirakawa, M Yoshida, K Nakao

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY　107　(1)　135-140　1997/01

    ISSN： 0009-9104

  151. REPRESSION OF CELL-CYCLE PROGRESSION BY ANTISENSE HMG2 RNA Peer-reviewed

    F YAMAZAKI, Y NAGATSUKA, H SHIRAKAWA, M YOSHIDA

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　210　(3)　1045-1051　1995/05

    DOI： 10.1006/bbrc.1995.1762 　

    ISSN： 0006-291X

  152. STIMULATION OF TRANSCRIPTION ACCOMPANYING RELAXATION OF CHROMATIN STRUCTURE IN CELLS OVEREXPRESSING HIGH-MOBILITY GROUP-1 PROTEIN Peer-reviewed

    Y OGAWA, S AIZAWA, H SHIRAKAWA, M YOSHIDA

    JOURNAL OF BIOLOGICAL CHEMISTRY　270　(16)　9272-9280　1995/04

    DOI： 10.1074/jbc.270.16.9272 　

    ISSN： 0021-9258

  153. EXISTENCE OF A TRANSCRIPTION FACTOR FOR THE HUMAN HMG2 GENE POSITIVELY RELATED TO THE LEVEL OF HMG2 MESSENGER-RNA IN THE CELLS Peer-reviewed

    H SHIRAKAWA, M YOSHIDA

    BIOCHEMISTRY　34　(8)　2521-2527　1995/02

    DOI： 10.1021/bi00008a016 　

    ISSN： 0006-2960

  154. STIMULATION OF TRANSCRIPTION IN CULTURED-CELLS BY HIGH-MOBILITY GROUP PROTEIN-1 - ESSENTIAL ROLE OF THE ACIDIC CARBOXYL-TERMINAL REGION Peer-reviewed

    S AIZAWA, H NISHINO, K SAITO, K KIMURA, H SHIRAKAWA, M YOSHIDA

    BIOCHEMISTRY　33　(49)　14690-14695　1994/12

    DOI： 10.1021/bi00253a006 　

    ISSN： 0006-2960

  155. STIMULATION OF DNA-DEPENDENT PROTEIN-KINASE ACTIVITY BY HIGH-MOBILITY GROUP PROTEIN-1 AND PROTEIN-2 Peer-reviewed

    F WATANABE, H SHIRAKAWA, M YOSHIDA, K TSUKADA, H TERAOKA

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　202　(2)　736-742　1994/07

    DOI： 10.1006/bbrc.1994.1992 　

    ISSN： 0006-291X

  156. STRUCTURE OF A GENE CODING FOR HUMAN HMG2 PROTEIN Peer-reviewed

    H SHIRAKAWA, M YOSHIDA

    JOURNAL OF BIOLOGICAL CHEMISTRY　267　(10)　6641-6645　1992/04

    ISSN： 0021-9258

  157. PRIMARY STRUCTURE OF NONHISTONE CHROMOSOMAL PROTEIN HMG2 REVEALED BY THE NUCLEOTIDE-SEQUENCE Peer-reviewed

    H SHIRAKAWA, K TSUDA, M YOSHIDA

    BIOCHEMISTRY　29　(18)　4419-4423　1990/05

    DOI： 10.1021/bi00470a022 　

    ISSN： 0006-2960

  158. The selective binding of HMG1 to the cruciform DNA structure and the subsequent resumption of transcription.

    Waga, S., Shirakawa, H., Mizuno, S., Yoshida, M.

    Nucleic acids symposium series　(22)　1990

  159. ANTIBIOTIC-INDUCED VITAMIN-K DEFICIENCY AND THE ROLE OF THE PRESENCE OF INTESTINAL FLORA Peer-reviewed

    H SHIRAKAWA, M KOMAI, S KIMURA

    INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH　60　(3)　245-251　1990

    ISSN： 0300-9831

  160. Establishment of primary vitamin K deficient mice and its use for menaquinones metabolism

    Komai, M., Shirakawa, H., Sato, H., Kimura, S.

    Vitamins　63　(5-6)　1989

  161. NEWLY DEVELOPED MODEL FOR VITAMIN-K DEFICIENCY IN GERMFREE-MICE Peer-reviewed

    M KOMAI, H SHIRAKAWA, S KIMURA

    INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH　58　(1)　55-59　1988

    ISSN： 0300-9831

Show all ︎Show first 5

Misc. 79

  1. Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness Not Only in Clinical Diagnosis, but Also in Unhealthy Dietary Lifestyle Improvements Peer-reviewed

    Michio Komai, Dan Takeno, Chiharu Fujii, Joe Nakano, Yusuke Ohsaki, Hitoshi Shirakawa

    Nutrients　16　(12)　1914-1914　2024/04/02

    Publisher: MDPI AG

    DOI： 10.20944/preprints202404.0078.v1 　

    eISSN： 2072-6643

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    Since the 1970s, the utility of nailfold capillaroscopy (NFC) in diagnosing rheumatological disorders such as systemic sclerosis has been well established. Further studies have also shown that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, and Alzheimer disease. In the past decade, nailfold capillary morphological changes have also been reported as symptoms of unhealthy lifestyle habits such as poor diet, smoking, sleep deprivation, and even psychological stress, all of which contribute to slow blood flow. Therefore, studying the relationships between the morphology of nailfold capillaries and lifestyle habits has a high potential to indicate unhealthy states or even pre-disease conditions. Simple, inexpensive, and non-invasive methods such as NFC are important and useful for routine medical examinations. The present study began with a systematic literature search of the PubMed database followed by a summary of studies reporting the assessment of morphological changes detected by NFC, and a comprehensive review of NFC’s utility in clinical diagnosis and improving unhealthy dietary lifestyles. It culminates in a summary of dietary and lifestyle health promotion strategy, assessed based on NFC and other related measurements that indicate healthy microvascular blood flow and endothelial function.

  2. 新規形態のビオチン塩の開発とその効果 Peer-reviewed

    塩沢浩太, 大崎雄介, 白川仁

    ビタミン　98　21-24　2024/01

  3. 乳汁中免疫グロブリン濃度の遺伝性と赤外分光スペクトル分析を用いた予測法の開発による抗病性育種への可能性

    佐竹有理, 桂哲平, 遠藤佑真, 庄涛, 浦川めぐみ, 中村武彦, 吉田岳, 馬場俊見, 北澤春樹, 白川仁, 野地智法, 麻生久, 佐藤正寛, 上本吉伸

    日本畜産学会大会講演要旨　131st　2023

    ISSN： 1342-4688

  4. 糖尿病と高血圧に対して期待されるビオチンの効果 Peer-reviewed

    大崎雄介, Afifah Zahra Agista, 白川仁

    ビタミン　96　474-476　2023

  5. Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease Peer-reviewed

    Hsin-Jung Ho, Hitoshi Shirakawa

    Cells　12　(1)　88-88　2022/12/25

    Publisher: MDPI AG

    DOI： 10.3390/cells12010088 　

    eISSN： 2073-4409

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    The kidney contains many mitochondria that generate ATP to provide energy for cellular processes. Oxidative stress injury can be caused by impaired mitochondria with excessive levels of reactive oxygen species. Accumulating evidence has indicated a relationship between oxidative stress and kidney diseases, and revealed new insights into mitochondria-targeted therapeutics for renal injury. Improving mitochondrial homeostasis, increasing mitochondrial biogenesis, and balancing mitochondrial turnover has the potential to protect renal function against oxidative stress. Although there are some reviews that addressed this issue, the articles summarizing the relationship between mitochondria-targeted effects and the risk factors of renal failure are still few. In this review, we integrate recent studies on oxidative stress and mitochondrial function in kidney diseases, especially chronic kidney disease. We organized the causes and risk factors of oxidative stress in the kidneys based in their mitochondria-targeted effects. This review also listed the possible candidates for clinical therapeutics of kidney diseases by modulating mitochondrial function.

  6. The role of vitamin K in cholestatic liver disease Peer-reviewed

    Halima Sultana, Michio Komai, Hitoshi Shirakawa

    Nutrients　13　(8)　2021/08

    DOI： 10.3390/nu13082515 　

    eISSN： 2072-6643

  7. High doses of biotin affect testicular morphology and spermatogenesis Peer-reviewed

    塩沢浩太, 大崎雄介, 白川仁

    ビタミン　94　(11)　557-559　2020/11

    ISSN： 0006-386X

  8. ビタミンKによる健康寿命の延伸

    白川 仁

    ビタミン　94　(2)　91-93　2020/02

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  9. 亜鉛投与法の違いによる摂食促進効果をラット脳視床下部メタボローム解析で明らかにする : Zinc-ome(ジンクオーム)の観点から—10周年記念特別企画 論文集(第2集)

    酒井 久美子, 西内 美香, 白川 仁, 駒井 三千夫

    亜鉛栄養治療 = Journal of zinc nutritional therapy　11　(1)　232-243,252　2020

    Publisher: 近畿亜鉛栄養治療研究会

    ISSN： 2187-574X

  10. 亜鉛投与法の違いによる摂食促進効果をラット脳視床下部メタボローム解析で明らかにする Zinc-ome(ジンクオーム)の観点から

    酒井 久美子, 西内 美香, 白川 仁, 駒井 三千夫

    亜鉛栄養治療　9　(2)　66-77　2019/03

    Publisher: 日本亜鉛栄養治療研究会

    ISSN： 2187-574X

    eISSN： 2187-9133

  11. 離乳後1週間のビオチンは膵島および膵β細胞を増殖させる

    塩沢 浩太, 白川 仁, 駒井 三千夫

    ビタミン　93　(2)　58-60　2019/02

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  12. フラボノイドおよびポリメトキシフラボノイドの腸内細菌による生体内変換

    堀籠 悟, 白川 仁, 駒井 三千夫

    ビタミン　93　(2)　61-65　2019/02

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  13. Anti-inflammatory effect of metabolites of dietary tryptophan via aryl hydrocarbon receptor

    Islam Jahidul, 白川 仁, 駒井 三千夫

    無菌生物　48　(2)　51-55　2018/12

    Publisher: 日本無菌生物ノートバイオロジー学会

    ISSN： 0910-0903

  14. A novel function of geranylgeraniol in regulating testosterone production. International-journal Peer-reviewed

    Ho H-J, Shirakawa H, Giriwono PE, Ito A, Komai M

    Biosci. Biotechnol. Biochem.　82　(6)　791-797　2018/06

    DOI： 10.1080/09168451.2017.1415129 　

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    Isoprenoids play widely differing roles in various physiological processes in animals and plants. Geranylgeraniol (GGOH) is an isoprenoid found in plants, and is an important metabolic derivative in the isoprenoid/cholesterol synthesis pathway. Earlier studies focused on GGOH's ability to improve the side effects of bisphosphonate therapy by regulating the mevalonate pathway. More recently, the mevalonate pathway-independent effects of GGOH have been described, including anti-inflammatory, anti-tumorigenic, and neuroprotective activities. It is noteworthy that GGOH regulates the steroidogenesis pathway in testis-derived I-10 tumor cells. Testosterone is a hormone produced via steroidogenesis in testicles and plays a role in fetal development and the male reproductive system. GGOH enhanced testosterone and progesterone (its precursor) levels in I-10 cells by activating adenylate cyclase via cAMP/PKA signaling, without altering phosphodiesterase activity. These findings highlight the potential benefits of GGOH as a therapeutic agent for low testosterone levels, such as late-onset hypogonadism in men.

  15. The Function of Geranylgeraniol Peer-reviewed

    白川 仁, 何 欣蓉, 駒井 三千夫

    オレオサイエンス　18　(3)　99-106　2018/03

    Publisher: 日本油化学会

    ISSN： 1345-8949

  16. Clarification of the mechanism involved in orexigenic action by oral zinc ingestion

    Komai, M., Goto, T., Ohinata, K., Kambe, T., Mayanagi, Y., Shirakawa, H.

    Yakugaku Zasshi　138　(8)　1011-1016　2018

    Publisher: The Pharmaceutical Society of Japan

    DOI： 10.1248/yakushi.17-00048-2 　

    ISSN： 0031-6903

  17. 消化器系癌患者における苦味受容体TAS2Rの遺伝子型解析

    八巻 美智子, 齋藤 弘貴, 磯野 邦夫, 後藤 知子, 白川 仁, 庄司 憲明, 佐藤 しづ子, 笹野 高嗣, 岡田 良, 工藤 克昌, 元井 冬彦, 海野 倫明, 駒井 三千夫

    日本栄養・食糧学会大会講演要旨集　71回　336-336　2017/04

    Publisher: (公社)日本栄養・食糧学会

  18. Energy homeostasis by peripheral serotonin

    Watanabe H, Rose M, Kanayama Y, Shirakawa H, Aso H

    Serotonin　2017/03/22

    Publisher: InTech, Rijeka, Croatia

    DOI： 10.5772/intechopen.68831 　

  19. Rice bran as a functional food: An overview of the conversion of rice bran into a superfood / functional food.

    Alauddin M, Islam J, Shirakawa H, Koseki T, Ardiansyah, Komai M

    Superfood and Functional Food - An Overview of Their Processing and Utilization　2017/03

    Publisher: InTech, Rijeka, Croatia

    DOI： 10.5772/66298 　

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    責任著者

  20. Menquinone-4 enhances steroidogenesis in testis derived tumor cells via the elevation of cAMP level. Peer-reviewed

    Ho H-J, Shirakawa H, Komai M

    Vitamin K2 - Vital for Health and Wellbeing　2017/03

    Publisher: InTech, Rijeka, Croatia

    DOI： 10.5772/63982 　

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    責任著者

  21. 酢酸：ヒストンのアセチル化修飾を介した遺伝子発現調節

    佐藤祥子, 白川仁

    ビタミン　91　(1)　57-61　2017/01

    Publisher: 日本ビタミン学会

    DOI： 10.20632/vso.91.1_57 　

    ISSN： 0006-386X

  22. ポリメトキシフラボノイドの血管機能調節作用

    堀籠悟, 白川仁, 駒井三千夫

    ビタミン　90　(12)　609-612　2016/11

    Publisher: 公益社団法人 日本ビタミン学会

    DOI： 10.20632/vso.90.12_609 　

  23. メナキノンカルボン酸誘導体の系統的合成と抗炎症および肝癌細胞増殖抑制作用

    藤井晋也, 清水章貴, 桂井朋子, 小口一起, 秦咸陽, 白川仁, 駒井三千夫, 小嶋聡一, 影近弘之

    ビタミン　90　253-260　2016/07

  24. Enhancement of testosterone production by vitamin K

    白川仁, 何欣蓉, 駒井三千夫

    ビタミン　90　(1)　3-8　2016/01

    Publisher: The Vitamin Society of Japan

    DOI： 10.20632/vso.90.1_3 　

    ISSN： 0006-386X

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    責任著者

  25. ビタミンKの生体内変換と生成したメナキノン－4の機能 Peer-reviewed

    白川仁, 桂井朋子, 駒井三千夫

    オレオサイエンス　14　(12)　547-553　2014/12

    Publisher: Japan Oil Chemists' Society

    DOI： 10.5650/oleoscience.14.547 　

    ISSN： 1345-8949

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    <p>Vitamin K is an essential factor for posttranslational modification (γ-glutamylcarboxylation) of vitamin K-dependent proteins including blood coagulation factors and bone matrix proteins. However, there are many reports regarding novel functions of vitamin K; inhibition of cell proliferation and induction of differentiation in tumor cells, and activation of nuclear receptor SXR/PXR. After ingestion from foods, vitamin K is converted to menaquinone-4, one of vitamin K2, which has geranylgeranyl moiety at 3 position of 2-methylnaphthoquinone, in various organs in human and rodent. UbiA prenyltransferase domain containing 1, UBIAD1, was identified as one of crucial enzyme for this conversion, but entire conversion process has still not elucidated completely. In this review, we described recent knowledge of menaquinone-4 conversion, novel functions of vitamin K, specially menaquinone-4, and discussed physiological meaning of menaquinone-4 conversion in tissues.</p>

  26. ビタミンKの抗炎症作用

    白川仁

    ビタミンKと疾患－基礎の理解と臨床への応用　120-127　2014/11

    Publisher: 医薬ジャーナル社

  27. 消化管内で生成する短鎖脂肪酸による糖代謝調節

    青山薫英, 白川仁, 駒井三千夫

    ビタミン　88　(8)　432-434　2014/09

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.88.8_432 　

    ISSN： 0006-386X

  28. 雑穀の健康機能性

    白川仁

    冷凍　89　462-468　2014/08

  29. ビタミンK欠乏食給餌が遺伝的糖尿病モデルマウスの膵臓および肝臓の遺伝子発現に及ぼす影響

    平原啓甫, 白川仁, 曽根英行, 桂井朋子, 後藤知子, 駒井三千夫

    日本栄養・食糧学会大会講演要旨集　68th　253-253　2014/04/30

    Publisher: (公社)日本栄養・食糧学会

  30. アトピー性皮膚炎の進展におけるペリオスチンの役割

    小口一起, 白川仁, 駒井三千夫

    ビタミン　86　(12)　685-686　2012/12

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.86.12_685 　

    ISSN： 0006-386X

  31. トリプトファン代謝物キヌレニンによるAHR シグナルの活性化

    佐藤祥子, 白川仁

    ビタミン　86　(10)　569-572　2012/09

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.86.10_569 　

    ISSN： 0006-386X

  32. ビタミンK

    白川仁, 桂井朋子, 駒井三千夫

    Functional Food　5　340-345　2012/09

  33. 2-III-25 糖尿病モデルマウスにおけるビタミンKが糖代謝に及ぼす影響(一般演題要旨,日本ビタミン学会第64回大会講演要旨)

    平原 啓甫, 白川 仁, 齋藤 正頼, Giriwono Puspo E., 桂井 朋子, 後藤 知子, 駒井 三千夫

    ビタミン　86　(4)　279-279　2012/04/25

    Publisher: 日本ビタミン学会

    ISSN： 0006-386X

  34. 2-V-15 ゲラニルゲラニオールはマウス精巣由来細胞においてテストステロン産生を促進する(一般演題要旨,日本ビタミン学会第64回大会講演要旨)

    白川 仁, 吉田 理紗, 伊東 あさぎ, Puspo Edi Giriwono, 駒井 三千夫

    ビタミン　86　(4)　288-288　2012/04/25

    Publisher: 日本ビタミン学会

    ISSN： 0006-386X

  35. ビタミンK

    白川仁, 桂井朋子, 駒井三千夫

    Functional Food　5　340-345　2012/04

  36. インスリン、グルカゴン分泌における亜鉛の関与

    後藤知子, 白川仁, 駒井三千夫

    ビタミン　86　(2)　87-89　2012/02

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.86.2_87 　

    ISSN： 0006-386X

  37. 最新ビタミン学講話 : ビタミン発見100周年を記念して(13)ビタミンK

    白川 仁, 桂井 朋子, 駒井 三千夫

    Functional food : 機能性食品の基礎から臨床へ　5　(4)　340-345　2012

    Publisher: フジメディカル出版

    ISSN： 1882-3971

  38. 2-I-33 Geranylgeraniol improves insulin sensitivity in KK-A^y mice fed high fat diet

    Giriwono Puspo Edi, Shirakawa Hitoshi, Hata Shuichi, Kuriyama Hiroki, Goto Tomoko, Komai Michio

    Vitamins　85　(4)　252-252　2011/04/25

    Publisher: The Vitamin Society of Japan

    ISSN： 0006-386X

  39. 学会見聞記 農芸化学会大会

    七谷 圭, 新谷尚弘, 後藤知子, 白川 仁, 都築 毅, 榎本 賢, 此木敬一, 小関卓也, 日出間 志寿, 稲葉 靖子, 宮内啓介, 矢部富雄

    バイオサイエンスとインダストリー　68　(4)　259-268　2010/07/01

    Publisher: バイオインダストリー協会

    ISSN： 0914-8981

  40. 味覚機能への亜鉛酵素「炭酸脱水酵素」の寄与

    駒井三千夫, 後藤知子, 大日向耕作, 白川仁

    Bio. Res. Trace Elements　21　38-42　2010

    DOI： 10.11299/brte.21.38 　

  41. 味覚などの多くの機能に重要な亜鉛「－炭酸水の刺激味を感ずる際に必要な亜鉛酵素：炭酸脱水酵素や食餌亜鉛シグナルの話－」

    駒井三千夫, 後藤知子, 大日向耕作, 白川仁

    ソフト・ドリンク技術資料　161　231-245　2010

  42. Occurrence, properties, and applications of feruloyl esterases

    Takuya Koseki, Shinya Fushinobu, Ardiansyah, Hitoshi Shirakawa, Michio Komai

    APPLIED MICROBIOLOGY AND BIOTECHNOLOGY　84　(5)　803-810　2009/10

    DOI： 10.1007/s00253-009-2148-8 　

    ISSN： 0175-7598

  43. 低濃度ダイオキシン類による肥満促進とアテローム性動脈硬化

    佐藤祥子, 白川仁, 駒井三千夫

    ビタミン　83　(7)　402-405　2009/08

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.83.7_402 　

    ISSN： 0006-386X

  44. 新しいGlaタンパク質ファミリー

    白川仁, 齋藤正頼, 佐藤祥子, 駒井三千夫

    ビタミン　83　(1)　17-18　2009/01

    Publisher: THE VITAMIN SOCIETY OF JAPAN

    DOI： 10.20632/vso.83.1_17 　

    ISSN： 0006-386X

  45. 2-IV-10 Attenuation of lipopolysaccharide (LPS) induced liver injury in rat by geranylgeraniol (GGOH) supplementation

    Giriwono Puspo Edi, Ohsaki Yusuke, Shirakawa Hitoshi, Hata Shuichi, Kuriyama Hiroki, Komai Michio

    Vitamins　82　(4)　298-298　2008/04/25

    Publisher: The Vitamin Society of Japan

    ISSN： 0006-386X

  46. [Effect of biotin ingestion on the improvement of hypertension in SHRSP].

    Michio Komai, Mari Watanabe-Kamiyama, Shin Kamiyama, Kousaku Ohinata, Kimiko Horiuchi, Yuji Furukawa, Hitoshi Shirakawa

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica　131　(4)　248-51　2008/04

    ISSN： 0015-5691

  47. Effect of biotin ingestion on the improvement of hypertension in SHRSP

    KOMAI Michio, WATANABE KAMIYAMA Mari, KAMIYAMA Shin, OHINATA Kousaku, HORIUCHI Kimiko, FURUKAWA Yuji, SHIRAKAWA Hitoshi

    Folia Pharmacologica Japonica　131　(4)　248-251　2008/04/01

    Publisher: The Japanese Pharmacological Society

    DOI： 10.1254/fpj.131.248 　

    ISSN： 1347-8397

  48. Neurophysiological study on the mechanism involved in the astringent taste formation by acidified soy protein

    MACHIDA Sho, FUKUNARI Mayuko, SAITO Tsutomu, SHIRAKAWA Hitoshi, KOMAI Michio

    The Japanese journal of taste and smell research　14　(3)　303-304　2007/12/01

    Publisher: The Japanese Association for the Study of Taste and Smell

    ISSN： 1340-4806

  49. Maternal zinc deficiency during lactation period modify the regulation system of NaCl preference of their developed pups

    KOMAI Michio, TANAKA Yasunori, TSUJIMURA Natsuki, GOTO Tomoko, SHIRAKAWA Hitoshi, TADANO Takeshi

    The Japanese journal of taste and smell research　14　(3)　301-302　2007/12/01

    Publisher: The Japanese Association for the Study of Taste and Smell

    ISSN： 1340-4806

  50. Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function

    Komai, M., Shirakawa, H.

    Clinical calcium　17　(11)　1663-1672　2007/11

  51. Conversion of vitamin K into menaquinone-4 in aminal

    白川仁, 大崎雄介, 駒井三千夫

    化学と生物　45　(9)　627-634　2007/09

    Publisher: Japan Society for Bioscience, Biotechnology, and Agrochemistry

    DOI： 10.1271/kagakutoseibutsu1962.45.627 　

    ISSN： 0453-073X

  52. 学会見聞記２００７年日本農芸化学会大会

    小林厚志, 永田裕二, 大崎雄介, 白川仁, 仲川清隆, 日出間志寿

    バイオサイエンスとインダストリー　65　(7)　360-363　2007/07/01

    Publisher: （財）バイオインダストリー協会

    ISSN： 0914-8981

  53. 酵母におけるビオチンによる遺伝子発現調節

    白川仁, 杉田弓美, 駒井三千夫

    ビタミン　81　(6)　248-250　2007/06

    Publisher: 公益社団法人 日本ビタミン学会

    DOI： 10.20632/vso.81.5-6_248 　

    ISSN： 0006-386X

  54. 2007年度日本農芸化学会大会（学会見聞記）

    小林厚志, 永田裕二, 大崎雄介, 白川仁, 仲川清隆, 日出間志寿

    バイオサイエンスとインダストリー　65　34-38　2007

  55. Effect of zinc deficiency on umami taste preference and monoamines levels in hypothalamus of SD rats

    MOTOYAMA Shigeki, GOTO Tomoko, SHIRAKAWA Hitoshi, TADANO Takeshi, KOMAI Michio

    The Japanese journal of taste and smell research　13　(3)　383-384　2006/12/01

    Publisher: The Japanese Association for the Study of Taste and Smell

    ISSN： 1340-4806

  56. Maternal zinc deficiency during lactation period modify their weanling and grown rats' NaCl preference regulation system

    TANAKA Yasunori, GOTO Tomoko, SHIRAKAWA Hitoshi, TADANO Takeshi, KOMAI Michio

    The Japanese journal of taste and smell research　13　(3)　385-386　2006/12/01

    Publisher: The Japanese Association for the Study of Taste and Smell

    ISSN： 1340-4806

  57. Erratum: Rice bran fractions improve blood pressure, lipid profile, and glucose metabolism in stroke-prone spontaneously hypertensive rats (Journal of Agricultural and Food Chemistry (2006) 54, (1914) DOI: 10.1021/jf068016h)

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Kousaku Ohinata, Katsumi Hashizume, Michio Komai

    Journal of Agricultural and Food Chemistry　54　9277　2006/11/29

    ISSN： 0021-8561

  58. Rice bran fractions improve blood pressure, lipid profile, and glucose metabolism in stroke-prone spontaneously hypertensive rats (vol 54, pg 1914, 2006)

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Kousaku Ohinata, Katsumi Hashizume, Michio Komai

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY　54　(24)　9277-9277　2006/11

    DOI： 10.1021/jf068016h 　

    ISSN： 0021-8561

  59. 経口摂取されたビタミンKの代謝物としてのメナジオン（ビタミンK3）

    白川仁, 大崎雄介, 駒井三千夫

    ビタミン　80　(10)　521-522　2006/10

    Publisher: (公社)日本ビタミン学会

    DOI： 10.20632/vso.80.10_521 　

    ISSN： 0006-386X

  60. コメ糠に含まれる成分の生活習慣病予防作用に関する研究

    駒井三千夫, 畠山英子, 白川仁

    感性福祉研究所年報　(7)　17-21　2006

  61. Recent topics in the studies of laboratory of nutrition, Tohoku University: Newly clarified function of vitamin K.

    Komai M, Ohsaki Y, Minegishi Y, Takumi N, Furukawa Y, Shirakawa H

    Tohoku J. Agricul. Res.　57　19-32　2006

  62. Novel function of vitamin K revealed by germfree rodent studies.

    Komai M, Shirakawa H, Ohsaki Y, Minegishi Y, Takumi N, Furukawa Y, Kimura S

    Journal of Germfree Life and Gnotobiology　36　1-11　2006

  63. 酸化ストレスによる神経細胞のアポトーシスを阻害するビタミンKの作用

    白川仁, 駒井三千夫

    ビタミン　78　(3)　147-150　2004/03

    Publisher: 公益社団法人 日本ビタミン学会

    DOI： 10.20632/vso.78.3_147 　

    ISSN： 0006-386X

  64. Tissue menaquinone-4 formation and its involvement in isoprenoids metabolism

    MINEGISHI YOSHIHIKO, OHSAKI YUSUKE, SHIRAKAWA HITOSHI, KOMAI MICHIO

    33　(2)　83-83　2003/12/01

    ISSN： 0910-0903

  65. 種を越えて存在しているビタミンK依存カルボキシラーゼ

    白川仁, 駒井三千夫

    ビタミン　77　(8)　470-473　2003/08

    DOI： 10.20632/vso.77.8_470 　

  66. Clarification of the conversion mechanism of vitamin K analogues to menaquinone-4 (MK-4)in the rats tissues without the participation of bacterial enzyme in the intestine

    KOMAI MICHIO, SHIRAKAWA HITOSHI, EJIRI MASAHIRO, HIWATASHI KAZUYUKI, OHSAKI YUSUKE, MIZUTANI TAKEO, FURUKAWA YUJI

    Journal of germfree life and gnotobiology.　32　(2)　94-97　2002/12/01

    Publisher: 日本無菌生物ノ-トバイオロジ-学会

    ISSN： 0910-0903

  67. DNAマイクロアレイによる栄養素の新しい作用の検索

    白川仁, 大崎雄介, 樋渡一之, 駒井三千夫, 古川勇次

    Boundary　17　(8)　30-32　2001/08

    Publisher: コンパス社

    ISSN： 0916-2402

  68. 新しいヌクレオソーム結合因子のクローニング (第2回「21世紀の境界領域研究を考えるシンポジウム」)

    白川 仁, 堀籠 悟, 駒井 三千夫

    バウンダリ-　16　(9)　28-29　2000/09

    Publisher: コンパス社

    ISSN： 0916-2402

  69. 新しいヌクレオソーム結合因子のクローニングとその性質

    白川仁, 堀籠悟, 駒井三千夫, 古川勇次

    Boundary　16　(9)　28-29　2000/09

  70. 神経系の発達におけるビタミンＫの関与

    白川仁, 駒井三千夫, 古川勇次

    ビタミン　74　(8)　447-449　2000/08

    DOI： 10.20632/vso.74.8_447 　

  71. The DNA bending machariism by HMG2 protein

    NAKAMURA Y., SHIRAKAWA H., YOSHIDA M.

    21　287-287　1998/12/01

  72. 転写におけるクロマチンの動的構造

    転写におけるクロマチンの動的構造

    臨床化学　27　(3)　108-116　1998/03

    Publisher: Japan Society of Clinical Chemistry

    DOI： 10.14921/jscc1971b.27.3_108 　

    ISSN： 0370-5633

  73. CLONING OF THE cDNA ENCODING PLASMA MEMBRANE H^+ -ATPase FROM AN ACIDOPHILIC RED ALGA Cyanidium caldarium

    OHTA Hisataka, SHIRAKAWA Hitoshi, UCHIDA Kouji, YOSHIDA Michiteru, MATUO Yuhsi, ENAMI Isao

    37　104-104　1996/03

    ISSN： 0032-0781

  74. マウスの腸内フローラによるメナキノン類の産生とその宿主への寄与の可能性

    駒井三千夫, 佐藤斉, 木村修一, 白川仁

    第5回ビタミンK機能セミナー（メディカルジャーナル社）　18-29　1990

  75. 真性のビタミンＫ欠乏マウスの作出とそのメナキノン類の動態研究への応用

    駒井三千夫, 白川仁, 佐藤斉, 木村修一

    ビタミン　63　(5)　229-242　1989/06

    Publisher: The Vitamin Society of Japan

    ISSN： 0006-386X

    More details Close

    Germfree animals are thought to be an useful tool to establish a primary vitamin K (K) deficient model not caused by K antagonists or antibiotics treatment, because of their lack of intestinal flora. By an improvement of dietary oil source as short as 8 days feeding, severe K deficient symptoms were occurred in Germfree-K-deficient diet fed group only, whereas not at all in Conventional-K-deficient one. From the HPLC analysis of MK-4 content in liver, it was suspected that the content of MK-4 which had been thought to be an important form of K was not necessarily paralleled with the degree of K deficiency. This tendency was also observed in case of sodium latamoxef-treated mice, i.e., the hepatic content of MK-6 rather than MK-4 might reflect the degree of K deficiency. It was shown that the administered MK-4 into the colon or cecum was actually absorbed, and the curable effect of MK-4 administration on K deficiency was confirmed by the results of hepatic PIVKA-II analysis and PT or APTT measurements.

  76. 腸内細菌とビタミンKについてーマウスのビタミンK欠乏症の発症への腸内フローラの関与ならびに大腸からのビタミンKの吸収について

    駒井三千夫, 深澤洋, 木村修一, 白川仁

    第4回ビタミンK機能セミナー（メディカルジャーナル社）　51-63　1989

  77. 2.ビタミンK欠乏モデルとその栄養生理的有用性(第223回会議研究発表要旨,脂溶性ビタミン総合研究委員会)

    木村 修一, 駒井 三千夫, 白川 仁

    ビタミン　60　(12)　586-586　1986/12/25

    Publisher: 日本ビタミン学会

    ISSN： 0006-386X

  78. 1-I-4 無菌マウスによるビタミンK欠乏の発症とビタミンKの生体内動態(第38回大会研究発表要旨,日本ビタミン学会)

    駒井 三千夫, 白川 仁, 木村 修一

    ビタミン　60　(7)　262-263　1986/07/25

    Publisher: 日本ビタミン学会

    ISSN： 0006-386X

  79. ビタミンK欠乏モデルとビタミンKの動態

    駒井三千夫, 白川仁, 木村修一

    第3回ビタミンK機能セミナー（メディカルジャーナル社）　28-35　1986

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Books and Other Publications 10

  1. 豆類の百科事典

    国分, 牧衛, 石本, 政男, 村本, 光二, 加藤, 淳, 谷口, 亜樹子

    朝倉書店　2024/05

    ISBN: 9784254400267

  2. 米の機能性食品化と新規利用技術・高度加工技術の開発

    白川仁

    2022/03

  3. 食品免疫学事典

    白川仁

    朝倉書店　2021/11

    ISBN: 9784254431261

  4. ビタミン・バイオファクター総合事典

    白川仁

    朝倉書店　2021/07

    ISBN: 9784254102925

  5. ビタミン・バイオファクター総合事典

    何欣蓉, 白川仁

    朝倉書店　2021/07

    ISBN: 9784254102925

  6. 基礎食品学

    白川仁

    アイ・ケイコーポレーション　2015/12

  7. 基礎栄養学

    白川仁

    アイ・ケイコーポレーション　2013/03

  8. 機能性食品の作用と安全性百科

    白川仁, 後藤知子, 仲川清隆

    丸善出版　2012

  9. 農学生命科学を学ぶための入門生物学

    白川仁

    東北大学出版会　2011/05/10

  10. ビタミン総合事典

    白川仁

    朝倉書店　2010/11/25

Show all Show first 5

Presentations 72

  1. 生体内変換型ビタミンKの新たな役割

    白川 仁

    日本栄養・食糧学会北海道支部・東北支部合同支部大会 シンポジウム　2024/12/07

  2. Novel function of vitamin K - the involvement of bile acid metabolism - Invited

    Hitoshi Shirakawa

    1st International Seminar on Food Science and Technology　2024/10/29

  3. Effects of the extract of rice bran fermented by fungi and lactic acid bacteria on life-style related disease models Invited

    HItoshi Shirakawa

    SIBAL - AJLAB 2024　2024/08/08

  4. Novel functions of vitamins for the health promotion. Invited

    Hitoshi Shirakawa

    The Symposium for Pharmaceutical Sciences between Tohoku University and National Yang Ming Chiao Tung University　2023/11/28

  5. Novel functions of vitamin K and biotin to extend healthy life expectancy. Invited

    Hitoshi Shirakawa

    National Seminar and Congress ISFFN 2023　2023/11/23

  6. The effect of fermented rice bran on lifestyle related diseases Invited

    Hitoshi Shirakawa

    2023/02/25

  7. 長寿時代の健康とビタミン Invited

    白川仁

    最先端エイジングセミナー　2022/08/04

  8. 我が国におけるビタミンK2 研究の進展と新たな 健康機能性 Invited

    白川 仁

    国際ビタミンK2 シンポジウム　2021/10/07

  9. ビタミンKの新たな作用と健康機能 Invited

    白川 仁

    日本農芸化学会2021年度大会　2021/03/20

  10. 芳香族炭化水素受容体を介した インドールによる抗炎症作用 Invited

    白川 仁, Islam Jahidul, Agista Afifah Zahra, 鈴木 玲, 大崎 雄介, 小関 卓也, 駒井 三千夫

    日本農芸化学会2021年度大会　2021/03/19

  11. イソプレノイドの健康増進効果〜ビタミンＫの場合 Invited

    白川 仁

    ビタミンB研究委員会 2020年度シンポジウム　2021/03/05

  12. 無菌生物で栄養学を研究する「ビタミン」 Invited

    白川 仁

    第54回日本無菌生物ノートバイオロジー学会総会　2021/01/21

  13. ビタミンKによるテストステロン合成増強 Invited

    白川 仁

    第11回テストステロン研究会　2020/10/09

  14. Recent studies in physiological functions and nutritional effects of food composition and functional food ingredients Invited

    Hitoshi Shirakawa

    THE 3rd INTERNATIONAL CONFERENCE ON FOOD SCIENCE AND ENGINEERING (ICFSE) 2020　2020/09/29

  15. The dietary ingredients show anti-inflammatory effects via aryl hydrocarbon receptor International-presentation Invited

    Hitoshi Shirakawa

    International Conference on Clinical Lipid Nutrition　2019/11/19

  16. Vitamin K regulates the gene expression of drug-metabolism and bile acid synthesis via pregnane X receptor. International-presentation Invited

    SHIRAKAWA Hitoshi

    International Symposium on Nutrition and Human Health　2018/11/02

  17. Emergence of novel function of vitamin K in pregnane X receptor humanized mice. Invited

    SHIRAKAWA Hitoshi

    2nd Inauguration Seminar 2018, Universitas Bakrie　2018/09/27

  18. Research collaboration of fermented rice bran for health promotion in Japan and Indonesia. International-presentation Invited

    SHIRAKAWA Hitoshi

    General Assembly and the Second International Symposium of JSPS Alumni Association of Indonesia.　2018/09/26

  19. 米糠の生活習慣病予防効果 Invited

    白川 仁

    日本畜産学会第123回大会 CFAI-CFMF合同シンポジウム2017「農免疫と菌類・微生物学のコラボダイナミズム創発に向けて」　2017/09/05

  20. Japan-Indonesia Joint Studies in TU Case 2: Graduate School of Agricultural Science International-presentation

    Hitoshi Shirakawa

    Tohoku University: Environmental Studies Seminar 2017 in ITB　2017/02/27

  21. Functional property of processed rice bran: application to the prevention of life-style related diseases.

    Hitoshi Shirakawa

    Open house symposium of the College of Nutrition, Taipei Medical University　2017/01/06

  22. ビタミンKの抗炎症作用

    第26回日本産婦人科・新生児血液学会学術集会 サテライトシンポジウム 第19回ビタミンKフォーラム　2016/07/01

  23. Nutraceuticals for the prevention of lifestyle-related diseases.

    42th Annual Meeting and Conference of Nutrition Society of Taiwan　2016/05/20

  24. 食品成分によるテストステロン産生の増強

    第70回日本栄養・食糧学会大会　2016/05/13

  25. Nutraceuticals for the prevention of lifestyle-related diseases International-presentation

    1st International Synposium of CFAI　2015/12/12

  26. ビタミンKによる性ホルモン産生促進

    日本ビタミン学会第67回大会　2015/06/05

  27. Effects of menaqauinone-4 and geranylgeraniol on testosterone production in testis-derived tumor I-10 cells. International-presentation

    Hsin-Jung Ho, Hitoshi Shirakawa, Risa Yoshida, Misato Maeda, Tomoko Goto, Michio Komai

    12th Asian Congress of Nutrition　2015/05/14

  28. In vivo study of processed soymilk containing ACE inhibitory peptides improved hypertension in spontaneously hypertensive rats. International-presentation

    Md Alauddin, Hitoshi Shirakawa, Kazuyuki Hiwatashi, Atsushi Shimakage, Saori Takahashi, Mamoru Shinbo, Michio Komai

    12th Asian Congress of Nutrition　2015/05/14

  29. Analysis of serotonin and its precursor tryptamine and tryptophan in commonly consumed fruits and vegetables in Japan International-presentation

    Jahidul Islam, Hitoshi Shirakawa, Thomas Kim Nguyen, Hisashi Aso, Michio Komai

    12th Asian Congress of Nutrition　2015/05/14

  30. Effect of biotin on steroidogenesis in cultured testis-derived tumor cells International-presentation

    Misato Maeda, Hitoshi Shirakawa, Hsin-Jung Ho, Tomoko Katsurai, Tomoko Goto, Michio Komai

    12th Asian Congress of Nutrition　2015/05/14

  31. アデノシン、AMPによるメタボリックシンドローム改善作用

    白川仁, Ardiansyah, 小関卓也, 稲川裕人, 樋渡一之, 高橋砂織, 秋山美展, 駒井三千夫

    第9回遺伝子栄養学研究会学術集会　2014/09/19

  32. Anti-metabolic activity and its mechanism of fermented barley extract in stroke-prone spontaneously hypertensive rats International-presentation

    Ardiansyah, Hitoshi Shirakawa, Puspo Edi Giriwono, Kazuki Oguchi, Kazuma Ueda, Hideki Hokazono, Kazuyuki Hiwatashi, Saori Takahashi, Shoko Sato, Michio Komai

    World Diabetes Congress 2013　2013/12/01

  33. 米糠および米糠由来物質の生活習慣病改善効果

    第16回日本補完代替医療学会学術集会　2013/11/30

  34. Enhanced production of testosterone by geranylgeraniol in mouse testis derived tumor cells International-presentation

    Risa Yoshida, Asagi Ito, Puspo Edi Giriwono, Tomoko Goto, Michio Komai

    20th International Congress of Nutrition　2013/09/15

  35. 米糠由来物質の抗メタボリックシンドローム作用

    白川仁, 駒井三千夫

    第46回日本栄養・食糧学会東北支部大会　2012/11/17

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  36. Geranylgeraniol supplementation suppresses LPS-induced NF-κB signal transducers activation in THP-1 cells and rats. International-presentation

    Puspo E. Giriwono, Hitoshi Shirakawa, Yusuke Ohsaki, Shuichi Hata, Hiroki Kuriyama, Shoko Sato, Tomoko Goto, Michio Komai

    BioMed Central meeting “Metabolism, diet and disease”　2012/05/29

  37. Germfree animal studies lead to the revelation of new functions of vitamin K. International-presentation

    Michio Komai, Hitoshi Shirakawa

    The Joint Meeting of The XVIIth International Symposium on Gnotobiology and The XXXIVth Congress of the Society for Microbial Ecology and Disease.　2011/11/20

  38. Administration of adenosine 5’-monophosphate has a novel effect on ameliorating hypertension, glucose, and lipid metabolism in stroke-prone spontaneously hypertensive rats. International-presentation

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Kazuyuki Hiwatashi, Saori Takahashi, Yoshinobu Akiyama, Michio Komai

    International Conference and Exhibition on Nutraceuticals and Functional Foods 2011　2011/11/14

  39. Fermented barley extract attenuates LPS induced inflammation and liver injury. International-presentation

    Kazuki Oguchi, Puspo Edi Giriwono, Hideki Hokazono, Hitoshi Shirakawa, Tomoko Goto, Michio Komai

    International Conference and Exhibition on Nutraceuticals and Functional Foods 2011　2011/11/14

  40. Anti-metabolic syndrome activity of Driselase-treated fraction of rice bran in stroke-prone spontaneously hypertensive rats International-presentation

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Michio Komai

    28th Int’l Rice Research Conference　2010/11/08

  41. Orally administered zinc increases food intake via vagus nerve signal transduction in SD rats. International-presentation

    Komai M, Ohinata K, Takemoto M, Kawanago M, Fushimi S, Shirakawa H, Goto T, Asakawa A

    第60回藤原セミナー Zinc signal and cellular functions　2010/10

  42. Effects of short-term zinc deficiency on salt preference in rats International-presentation

    Tomoko Goto, Hitoshi Shirakawa, Michio Komai

    第60回藤原セミナー Zinc signal and cellular functions　2010/10

  43. Gnotobiology: Current Situation and Perspectives --- Possible Renaissance International-presentation

    Michio Komai, Hitoshi Shirakawa

    32nd International Congress of the Society for Microbial Ecology and Disease　2009/10/29

  44. Anti-metabolic syndrome activity of adenosine in stroke-prone spontaneously hypertension rats International-presentation

    Ardiansyah, Hitoshi Shirakawa, Takuya Koseki, Michio Komai

    3rd International Congress on Prediabetes and the Metabolic Syndrome　2009/04/01

  45. Oral administration of L-tryptophan is effective to improve glucose metabolism and hypertension in stroke-prone spontaneously hypertension rats International-presentation

    Ardiansyah, H Shirakawa, T Koseki, Y Shiono, T Murayama, M Komai

    3rd International Congress on Prediabetes and the Metabolic Syndrome　2009/04/01

  46. Menaquinone-4, a vitamin K2 analogue, suppresses inflammation through the inhibition of NFkB activation International-presentation

    PE Giriwono, Y Ohsaki, H Shirakawa, A Miura, S Sato, T Goto, M Komai

    3rd International Congress on Prediabetes and the Metabolic Syndrome　2009/04/01

  47. DNAマイクロアレイによる遺伝子解析の特色

    白川仁

    第62回日本栄養食糧学会 イブニングセミナー 「若手研究者のための栄養・食糧学技術セミナー」　2008/05/03

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  48. Dietary vitamin K ameliorates the reduction of testosterone production by the administration of LPS in rat testis International-presentation

    Hitoshi Shirakawa, Naofumi Takumi, Yusuke Ohsaki, Toshiro Sato, Michio Komai

    10th Asian Congress of Nutrition　2007/09/09

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  49. Identification of novel physiological effect of oral administration of ferulic acid on hepatic gene expression in stroke-prone spontaneously hypertensive rats International-presentation

    Ardiansyah, Yusuke Ohsaki, Hitoshi Shirakawa, Michio Komai

    10th Asian Congress of Nutrition　2007/09/09

  50. Metallothionein gene expression was up-regulated by the aryl hydrocarbon receptor International-presentation

    Shoko Sato, Hitoshi Shirakawa, Michio Komai

    10th Asian Congress of Nutrition　2007/09/09

  51. Regulation of gluconeogenic gene expression by biotin in rats and hepatoma cells International-presentation

    Yumi Sugita, Hitoshi Shirakawa, Michio Komai

    10th Asian Congress of Nutrition　2007/09/09

  52. 薬理量ビタミン類の新規機能とメタボリックシンドロームの予防

    駒井三千夫, 白川仁

    第80回 日本薬理学会年会　2007/03/15

  53. Effects of water extract of Javanese pepper (Piper retrofractum Vahl.) on lipid metabolism in stroke-prone spontaneously hypertension rats. International-presentation

    Sedarnawati Yasni, Hitoshi Shirakawa, Michio Komai

    The 12th International Symposium on SHR -Genetics of Experimental and Human Hypertension in Relation with Environmental Factors　2006/10

  54. DRISELASE-TREATED FRACTION OF RICE BRAN IS EFFECTIVE TO IMPROVE BLOOD PRESSURE AND LIPID METABOLISM IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS International-presentation

    Ardiansyah, Hitoshi Shirakawa, Michio Komai

    The 12th International Symposium on SHR -Genetics of Experimental and Human Hypertension in Relation with Environmental Factors　2006/10

  55. Enhanced expression of metallothionein gene mediated with the aryl hydrocarbon receptor International-presentation

    Shoko Sato, Hitoshi Shirakawa, Michio Komai

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress　2006/06/18

  56. Involvement of nucleosome binding protein Nsbp1 in the gene expression of placental lactogen in placental cells. International-presentation

    Hitoshi Shirakawa, Michio Komai

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress　2006/06/18

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  57. Biotin represses gluconeogenic gene expression by down-regulation of transcriptional factors in rats and hepatoma cells. International-presentation

    Yumi Sugita, Hitoshi Shirakawa, Michio Komai

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress　2006/06/18

  58. Anti-inflammatory effects of vitamin K in LPS administrated rats. International-presentation

    Yusuke Ohsaki, Hitoshi Shirakawa, Kazuyuki Hiwatashi, Yuji Furukawa, Takeo Mizutani, Michio Komai

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress　2006/06/18

  59. ビタミンの新規作用の検索

    白川仁

    平成１７年度食科学フォーラム（秋田県総合食品研究所主催）　2006/01/18

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  60. ビタミンＫの新規作用の検索

    白川仁, 駒井三千夫

    第4回生体キノン研究会　2005/09/16

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    本人の講演

  61. ビタミンの新規作用の検索

    白川仁, 駒井三千夫

    日本食品科学工学会第52回大会　2005/08/31

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  62. Recent advances in physiological function of menaquinone-4 (MK-4), a unique vitamin K2 not derived from intestinal microflora International-presentation

    Michio Komai, Hitoshi Shirakawa

    The XVth Int. Symp. on Gnotobiology　2005/06/20

  63. Non-bacterial synthesized menaquinone-4 (vitamin K2) is a key involved in testicular steroid metabolism International-presentation

    Hitoshi Shirakawa, Yusuke Ohsaki, Yoshihiko Minegishi, Michio Komai

    The XVth Int. Symp. on Gnotobiology　2005/06/20

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  64. Clarification of novel functions of vitamin K using genome-wide expression analysis in liver of germfree rats International-presentation

    Yusuke Ohsaki, Hitoshi Shirakawa, Michio Komai

    The XVth Int. Symp. on Gnotobiology　2005/06/20

  65. Effects of marginal zinc deficiency on NaCl preference and oxytocin secretion in SD rats International-presentation

    Tomoko Goto, Michio Komai, Hitoshi Shirakawa

    Association for Chemoreception Sciences, XXVIIth Annual Meeting　2005/04/13

  66. ビタミンＫの新しい作用

    白川仁

    第38回日本栄養・食糧学会東北支部会　2004/10/23

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  67. 無菌動物を使用したビタミンKの新規作用の検索

    白川 仁, 大崎雄介, 峯岸慶彦, 駒井三千夫

    第37回日本無菌生物ノートバイオロジー学会　2004/01/27

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  68. メナキノン-４（ビタミンK2）の生体内変換生成と新しい生理機能

    駒井三千夫

    第298回脂溶性ビタミン総合研究委員会「故勝井五一郎顧問メモリアルシンポジウム」　2002/12/06

  69. メナキノン-４（ビタミンK2）の組織内生成機構の解析

    駒井三千夫

    第5回ビタミンK&Bone研究会　2002/02/23

  70. Biotin improves insulin resistance in Otsuka Long-Evans Tokushima fatty (OLETF) rats with NIDDM International-presentation

    Michio Komai

    Int. Symp. on Glycemic Carbohydrate and Health, ILSI　2001/11/20

  71. The effect of food Ingredient from Melinjo seed extract on nonalcoholic fatty liver disease in mice Invited

    Hitoshi Shirakawa

    2nd International Conference for Smart Agriculture, Food, and Environment (ICSAFE)　2021/11/04

  72. The Effect of Food Ingredient in Mice Model on Nonalcoholic Fatty Liver Disease (NAFLD) Invited

    Hitoshi Shirakawa

    ISNFF International Virtual Semina;Traditional Roots of;Functional Foods;Nutraceuticals to Serve;Human Wellbeing　2021/10/16

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Industrial Property Rights 25

  1. 抗炎症剤

    山田 耕太郎, 櫻井 英知, 駒井 三千夫, 白川 仁, 中村 圭佑, ギリウノ プスポ エディ, 植田 一馬

    特許第7216966号

    Property Type: Patent

  2. ゲノム安定性増強剤

    生田 智樹, 福島 忍, 立藤 智基, 吉岡 研一, 白川 仁

    特許第7116960号

    Property Type: Patent

  3. プロゲステロン産生促進剤

    中山 優也, 稲川 裕人, 平本 茂, 池本 裕之, 駒井 三千夫, 白川 仁, 何 欣蓉

    特許第6964416号

    Property Type: Patent

  4. 肝臓機能及び/又は膵臓機能の改善剤

    駒井 三千夫, 白川 仁, 山田 耕太郎, 櫻井 英知, 植田 一馬, ギリウノ プスポ エディ

    特許第6456833号

    Property Type: Patent

  5. テストステロン増加剤

    駒井 三千夫, 白川 仁, 大崎 雄介, 工 直史, 伊藤 あさぎ, 佐藤 俊郎, 小崎 瑠美

    特許第5110478号

    Property Type: Patent

  6. ゲノム安定性増強剤

    生田 智樹, 福島 忍, 立藤 智基, 吉岡 研一, 白川 仁

    Property Type: Patent

  7. 肝臓機能及び/又は膵臓機能の改善剤

    駒井 三千夫, 白川 仁, 山田 耕太郎, 櫻井 英知, 植田 一馬, ギリウノ プスポ エディ

    Property Type: Patent

  8. テストステロン増加剤

    駒井 三千夫, 白川 仁, 大崎 雄介, 工 直史, 伊藤 あさぎ, 佐藤 俊郎, 小崎 瑠美

    Property Type: Patent

  9. ジペプチドを含有する医薬組成物

    山田 耕太郎, 櫻井 英知, 佐藤 健司, 江島 晃佳, 駒井 三千夫, 白川 仁, 佐久間 航

    Property Type: Patent

  10. プロゲステロン産生促進剤

    中山 優也, 稲川 裕人, 平本 茂, 池本 裕之, 駒井 三千夫, 白川 仁, 何 欣蓉

    Property Type: Patent

  11. 肝臓機能及び/又は膵臓機能の改善剤

    駒井 三千夫, 白川 仁, 山田 耕太郎, 櫻井 英知, 植田 一馬, ギリウノ, プスポ エディ

    Property Type: Patent

  12. 組換体昆虫味ニューロン発現系

    駒井 三千夫, 白川 仁, 後藤 知子, 磯野 邦夫, 安達 良太, 森田 ひろみ, 佐々木 優子, 古山 昭

    Property Type: Patent

  13. テストステロン増強剤

    駒井 三千夫, 白川 仁, ギリウノ プスポ エディ, 伊東 あさぎ, 畠 修一

    Property Type: Patent

  14. テストステロン増強剤

    駒井 三千夫, 白川 仁, ギリウノ, プスポ エディ, 伊東 あさぎ, 畠 修一

    特許第5382512号

    Property Type: Patent

  15. 血漿アスパラギン酸アミノトランスフェラーゼ及びアラニンアミノ基転移酵素生成抑制剤

    駒井 三千夫, 白川 仁, ギリウノプスポエディ, 大崎雄介, 栗山宏樹, 畠修一

    Property Type: Patent

  16. ルペオール含有医薬組成物、食品及び飼料

    畠 恵司, 佐々木 裕樹, 河原崎 哲, 菅原 美貴子, 駒井 三千夫, 白川 仁, アルディアンシャー

    Property Type: Patent

  17. ルペオール含有医薬組成物、食品及び飼料

    畠 恵司, 佐々木 裕樹, 河原崎 哲, 菅原 美貴子, 駒井 三千夫, 白川 仁, アルディアンシャー

    特許第5428000号

    Property Type: Patent

  18. 血漿アスパラギン酸アミノトランスフェラーゼ及びアラニンアミノ基転移酵素生成抑制剤

    駒井 三千夫, 白川 仁, ギリウノ プスポエディ, 大崎 雄介, 栗山 宏樹, 畠 修一

    Property Type: Patent

  19. テストステロン増加剤

    駒井 三千夫, 白川 仁, 大崎雄介, 工直史, 伊東あさぎ

    Property Type: Patent

  20. フェルラ酸の抽出方法および疾患の予防食品および疾患の予防薬品

    駒井 三千夫, 白川 仁, アルディアンシャ, 橋爪 克己, 小関 卓也

    Property Type: Patent

  21. 生活習慣病改善食品および生活習慣病治療薬

    駒井 三千夫, 白川 仁

    Property Type: Patent

  22. 対象物に含まれるダイオキシン類の評価方法及びマイクロアレイ

    駒井 三千夫, 白川 仁, 佐藤 祥子, 戸笈 修, 山藤 憲明

    Property Type: Patent

  23. 対象物に含まれるダイオキシン類の評価方法及びマイクロアレイ

    駒井 三千夫, 白川 仁, 佐藤 祥子, 戸笈 修, 山藤 憲明

    Property Type: Patent

  24. 自己免疫疾患の診断薬

    尾▲さき▼ 承一, 傍島 淳子, 上▲すぎ▼ 裕子, 中尾 一和, 吉田 充輝, 白川 仁, 小坂田 史雄

    特許第3267893号

    Property Type: Patent

  25. 自己免疫疾患の診断薬

    尾▲さき▼ 承一, 傍島 淳子, 岡崎 貴裕, 上▲すぎ▼ 裕子, 田中 真生, 中尾 一和, 吉田 充輝, 白川 仁, 小坂田 史雄

    特許第3472048号

    Property Type: Patent

Show all Show first 5

Research Projects 65

  1. 米糠抽出物による生活習慣病予防効果 Competitive

    System: Cooperative Research

    2003/10 - Present

  2. ビオチンの生活習慣病善作用 Competitive

    System: Grant-in-Aid for Scientific Research

    1999/09 - Present

  3. Molecular-nutritional analysis of vitamin K and isoprenoids Competitive

    System: Grant-in-Aid for Scientific Research

    1999/09 - Present

  4. Structure and function of HMG chromosomal proteins Competitive

    System: The Other Research Programs

    1988/04 - Present

  5. 生体内変換型ビタミンKによる抗老化作用とその作用機序に関する研究

    白川 仁, 大崎 雄介, Afifah Zahra・Agista, 何 欣蓉

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  6. 潜在的ビタミンB6欠乏による腎障害増悪機序の解明

    大崎 雄介, 白川 仁, 森 建文

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  7. Analysis of genetic polymorphisms of bitter taste receptor TAS2R38 and glutathione-S-transferase (GST), and its relationship with eating habits in Japanese megabank database

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2023/04/01 - 2026/03/31

  8. 牛乳房炎発症予防法と抗病性育種の開発事業

    芳賀聡, 上本吉伸, 麻生久, 庄涛, 北澤春樹, 白川仁, 佐藤幹, 戸部隆太, 阪谷美樹, 三輪雅史, 櫛引史郎, 福田純子, 浅野貴史, 諏訪久仁子, 渡邊康平, 石井亮一, 吉田周平, 馬場俊見, 後藤裕作, 横井允雄

    Offer Organization: 公益財団法人 全国競馬・畜産振興会 (JRL）

    System: 令和５年度日本中央競馬会畜産振興事業

    Institution: 東北大学

    2023/08 - 2026/03

  9. 苦味受容体を介した苦味成分の新たな健康機能性

    白川 仁, 大崎 雄介, Afifah Zahra・Agista

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2023/06/30 - 2025/03/31

  10. うま味感受性を利用したフレイルとサルコペニア肥満の攻略法の開発ー骨格筋量の改善ー

    佐藤 しづ子, 菊池 雅彦, 庄司 憲明, 駒井 三千夫, 飯久保 正弘, 白川 仁, 島崎 伸子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  11. The study for the augmentation of happiness via food selection behavior and mental by subjective and objective evaluations

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2022/04/01 - 2025/03/31

  12. 魚類における酸化的ストレスの評価に特化したバイオマーカーの開発と健魚育成への応用

    中野 俊樹, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2025/03/31

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    ［背景と目的］ 魚類はローカルとグローバルな要因が複合した環境ストレスを受け、それは生存や成長などに影響を及ぼす。魚類は哺乳類に比べ絶食に強いことが知られているが、その耐性メカニズムについては不明な点が多い。今年度は、短期間の絶食がギンザケの生化学的なパラメーターに及ぼす影響を調べ、変動するパラメーターのストレスマーカーとしての有効性について検討した。 [方法] 1．材料：ギンザケ (Oncorhynchus kisutch) を馴致後、対照区と絶食区に分け2週間飼育した。その後組織（肝臓、普通筋、腸）、血液を採取した。2．生化学的パラメーターの測定：ストレスタンパク質（ヒートショックプロテイン (HSP) 70）、グルタチオン（GSH）レベル、血漿成分などを定法により測定した。 [結果および考察] 1．HSP70の発現：絶食により肝臓におけるHSP70の発現量は有意に増加した。2． GSHレベル：肝臓、筋肉、腸、血漿のいずれについても変化はなかった。３．血漿成分：グルコースは絶食により有意に増加した。一方、トリグリセリドは絶食区で有意に減少した。以上のことより、2週間の絶食はストレスを誘発するが、個体に及ぼす影響は小さいと推察され、絶食に対する耐性が強いことが窺われる。そしてストレスのマーカーとしては、組織のHSP70や血漿のグルコースや脂質成分が有効なことが示唆された。今後はより長期間の絶食処理を施し、それが各種生化学的パラメーターに与える影響を調べる必要がある。

  13. Increasing effect of cyclophilin A on somatic cell counts in milk of dairy cow

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2021/04/01 - 2024/03/31

  14. 脳内活性型ビタミンKの認知機能増強作用と作用機序の解析

    白川 仁, 大崎 雄介, SULTANA HALIMA, 何 欣蓉

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    ビタミンK（VK）は、血液凝固因子やオステオカルシンなどの骨タンパク質を活性化させるγ-グルタミルカルボキシラーゼの補因子として、必須な因子である。我々は、緑色野菜に含まれるVK1や発酵食品、動物性食品に含まれるVK2を摂取している。VKの生体内分布をみると骨や肝臓のほかに、膵臓、精巣、脳などにも存在しているが、各組織におけるVKの役割は未だ十分に明らかになっていない。本研究は、脳におけるVK、特にVK2のひとつであるメナキノン-4（MK-4）の作用を明らかにすることを目的とした。本年度は、MK-4の脳における抗炎症作用を明らかにするため、ミクログリアと神経細胞の共培養系での評価を行うとともに、炎症誘発認知症モデルにおいて、VK給餌の影響を解析した。 マウス由来株化ミクログリアをリポポリサッカライド（LPS）で刺激して、その培養上清を採取した。これを用いて、マウス海馬由来神経細胞を培養すると、細胞死が誘発され、ミクログリアからLPS刺激により神経細胞死を誘導する因子が放出されると考えられた。LPS刺激前にミクログリアをMK-4の側鎖構造体であるゲラニルゲラニオール（GGOH）で処理すると、神経細胞の細胞死が抑制された。このことから、GGOHはLPSにより誘導される炎症を抑制し、神経細胞死を引き起こす因子の発現を抑制することが示唆された。 LPSの投与によって起こる記憶障害をオープンフィールド試験、受動的回避行動試験によって評価した。VK1およびMK-4を給餌したマウスとコントロール食マウスとの間で、2つの試験結果に差は見られなかった。一方、LPSにより大脳、海馬のNFκBの発現量が上昇したが、MK-4の給餌によって有意に低下した。このことから、MK-4は脳内で起こる炎症を低下させて神経細胞死を抑制することが示唆された。

  15. Development of therapeutic strategy against congestive heart failure by food ingredients.

    OHSAKI Yusuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2020/04/01 - 2023/03/31

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    The purpose of this study was to establish strategies for prevention and improvement of congestive heart failure, associated fluid retention, and organ damage by searching for food ingredients that can alleviate renal damage caused by congestion. Unilateral renal congestion model rats were created by occuluding the left renal vein of normal rats with a silver clip. It has been shown that some of the renal injury marker genes induced by blood stasis are significantly reduced when certain food components are administered to this model rat in drinking water or by forced oral administration. Two analogues of this food component were also examined in a similar manner, suggesting that they may at least partially alleviate congestion-induced renal damage. These results indicate that certain food components has a possibility to improve renal injury induced by congestive heart failure.

  16. 妊娠期ラットの潜在的亜鉛欠乏が育児行動およびホルモン分泌に及ぼす影響

    後藤 知子, 白川 仁, 駒井 三千夫

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 宮城学院女子大学

    2017/04/01 - 2023/03/31

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    我が国では近年、食生活の偏りなどにより潜在的な亜鉛欠乏が増えているといわれている。必須微量元素のひとつである亜鉛は、胎児の発育にも必要であり、妊娠期は亜鉛摂取量を増やすことが推奨されている。しかし、若年女性では「やせ」の割合が高いことが報告されており、また妊娠期は悪阻などによる食欲不振を呈することも多いことから、妊娠期の潜在的亜鉛欠乏は多いと考えられる。妊娠期の重篤な亜鉛欠乏では遷延分娩・低出生体重児の出産などが報告されてきたが、妊娠期の潜在的亜鉛欠乏が育児行動に及ぼす影響は明らかではない。うつ病患者で血清亜鉛濃度が低下していることも報告されており、妊娠期・授乳期の潜在的亜鉛欠乏に起因し産後うつを発症する可能性も考えられる。しかし妊娠期の潜在的亜鉛欠乏がホルモン分泌に及ぼす影響も明らかではない。本研究ではこれまで、妊娠期ラットの潜在的亜鉛欠乏が育児行動・ホルモン分泌に及ぼす影響を明らかにするため、妊娠期に亜鉛添加食または低亜鉛食を給餌した亜鉛添加食群と低亜鉛食群を設けて検討し、妊娠期の潜在的亜鉛欠乏ラットで育児放棄様行動（授乳を行わない、接触の欠如など）が観察された個体を認めた。また育児行動変化の機構を探るため、産後（授乳期）ラットの血漿オキシトシン・コルチコステロン濃度をELISA法にて測定した結果、亜鉛添加食群に比べ低亜鉛食群で、血漿コルチコステロン濃度は有意に高く、血漿オキシトシン濃度は低い傾向が認められた。妊娠期の低亜鉛食群でコルチコステロン分泌の上昇が示唆されたことから、妊娠期の潜在的亜鉛欠乏でストレス応答が生じた可能性が考えられた。また、妊娠期の潜在的亜鉛欠乏によるオキシトシン分泌低下が育児放棄様行動の一因となる可能性も考えられた。しかし、妊娠期ラットの育児行動・ホルモン分泌は個体差が大きいことを考慮し、更なる検討が必要であり今後の課題である。

  17. Elucidation of Improvement of quolity of life (QOL) in the aged subjects through oral zinc ingestion

    KOMAI MICHIO

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    The present research showed that carbonic anhydrase (CA) activity and zinc concentration in saliva were lower in taste disorder patients than healthy subjects. By using data-independent acquisition (DIA)-mass spectrometry (MS)-based proteomic analysis in single-shot liquid chromatography (LC)-MS/MS system, we detected more than 1600 proteins in saliva of taste disorder patients and healthy subjects (outsourced analysis by Kazusa DNA Research Institute), and found out that CAVI was major protein which was under-expressed in taste disorder patients than healthy subjects. Moreover, the present analysis of genetic polymorphism of CAVI revealed the protein structure of CAVI could contribute the important role in maintaining normal taste function.

  18. Mechanism of action of oxidative environmental stress on fish health and its control based on scientific evidence

    Nakano Toshiki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2018/04/01 - 2022/03/31

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    Fish are often subjected to environmental stress. This stress can affect their growth. In this study, coho salmon were fasted or given the antibiotic oxytetracycline (OTC) to investigate the effects on biochemical parameters. The expression level of HSP 70 in the liver was increased by fasting and OTC administration. Tissue glutathione levels were unchanged by fasting, whereas OTC treatment increased them in the liver. As for plasma components, fasting and OTC administration increased glucose level and slightly changed lipid components. These findings suggest that fasting and OTC administration induces stress, however the effect of fasting on the individual is not so large. It was also suggested that antioxidative substances would be useful to reduce the stress in fish body due to environmental stress such as chemical stress.

  19. Cancer risk assessment study on gene polymorphism of bitter taste receptor TAS2R38 and glutathione-S-transferase by analyzing ToMMo data

    KOMAI Michio

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Research (Exploratory)

    Institution: Tohoku University

    2018/06/29 - 2020/03/31

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    Type 2 taste receptor (TAS2R) genes encode bitter-taste receptors, and it has been said that TAS2R38 can detect bitter substances in cruciferous vegetables and then suppress their intake by controlling gustatory or digestive response. The major haplotypes in TAS2R38 involve three non-synonymous, closely linked SNPs (single nucleotide polymorphisms), leading to three amino acid substitutions (A49P, V262A and I296V) and resulting in a PAV or AVI allele, and the allele frequency of PAV/AVI was 0.57/0.43 in this study. Moreover, we identified 5 haplotypes with minor alleles, and these subjects were totally 16 out of 2047 Japanese ToMMo subjects. From the questionnaire analyses of BMI (body mass index), the vegetables and drinking frequency in the three major TAS2R38 genotypes (AVI/AVI, AVI/PAV and PAV/PAV), there was no correlation in BMI at all, however, a significant difference in alcohol intake frequency was observed among the genotype groups, by the Contingency Table analysis.

  20. Novel function of menaquinone-4 in brain

    SHIRAKAWA HITOSHI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2017/04/01 - 2020/03/31

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    Naturally occurring vitamin K (VK) is phylloquinone and menaquinones. A part of ingested VK from the diet is converted to menaquine-4, but the biological meaning of this conversion has not been fully elucidated specially in brain. In this study, we analyzed the role of menaquinone-4 on the activation of protein kinase A and the suppression of inflammation using cognition impaired mice, normal rats and cultured microglia. Feeding of VK deficient diet to dementia model mice enhanced cognition impairment. VK supplemented diet in normal rats activated protein kinase A, and elevated the expression of neurotrophic factor in hippocampus. Menaquinone-4 suppressed lipopolysaccharide-induced inflammatory cytokine expression in mouse derived microglia via the inhibition of activation NF kappa B. These results lead to be understood the biological importance of VK conversion in brain.

  21. An Action Research on Social Implementatin of "Food & Agricultural Immunology" by Integration of Social and Natural Sciences

    Fuyuki Katsuhito, Chiba Yuki, Li Zhihang, Takahashi Hideki, Kitazawa Haruki, Takahashi Keisuke, Shirakawa Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2016/04/01 - 2019/03/31

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    Receiving consumer concerns about food safety, Tohoku University is performing research focused on food and agricultural immunology. Agricultural immunology is a general term for new technologies that realize healthy fostering of agricultural and livestock products by strengthening immune functions. However, "food & agricultural immunology" has not been yet known for people. Therefore, it is not clear whether consumers accept this technology or not. And so we try to examine consumer's preference for immune-health promoted pork (Lactic pork) which is newly developed food technology by Tohoku University. Using 300 Japanese respondents' data, we estimated individual preference for pork attributes. The main findings are as follows. 1. Consumer accept "Lactic" new food technology. 2. Evaluation on "Japan" pork is high. 3. Brand lover tends to choose "Lactic" pork. 4. Those who concern "Normal" pork prefer "Lactic" pork. 5. Rich people tends to concern "Normal" pork more.

  22. Genetic polymorphism of bitter taste receptor TAS2R and hepatic detoxification enzyme GST.

    Komai Michio, ISONO KUNIO, YAMAKI MICHIKO

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2015/04/01 - 2017/03/31

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    The involvement of bitter taste receptor, TAS2Rs in cancers has not been well understood. So, we conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the digestive cancer. As a results, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among control subjects, which indicates that the AVI/AVI genotype for TAS2R38 was therefore considered to increase cancer risk.

  23. A study on the mechanisms of energy production in super salmon and its appl ication for cultured fish

    NAKANO TOSHIKI, DEVLIN R. H., SOGA TOMOYOSHI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    Growth in fish is regulated by the growth hormone (GH)-insulin-like growth factor (IGF)-I axis. Little is known concerning the in vivo levels of metabolites, energy production and the mechanism of enhancement of growth in GH transgenic fish. The present study examined the features of GH transgenic coho salmon (Oncorhynchus kisutch) by metabolomic and mitochondrial function analysis. The difference found between transgenic (T) and non-transgenic (NT) fish was that glycolysis metabolite levels changed in the muscle of transgenic fish. The feature of metabolites in T fish which were fully fed after ration-restriction was not similar to that in fully-fed T fish. Mitochondrial function in the muscle of T fish was found to be promoted by GH transgenesis. The results suggest that GH transgenesis can improve the metabolic pathway and mitochondrial function associated with rapid growth.

  24. Effect of activated vitamin K analogue on endocrine function

    SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    Vitamin K is the micronutrient which is essential for blood coagulation system and bone metabolism in animals. The distribution of vitamin K is not only restricted in liver and bone, but also other organs including brain, gonadal tissues and pancreas. However, the functions of vitamin K in those tissues are remaining to be clarified. In this study, we analyzed the effect of vitamin K on insulin secretion from pancreatic beta cells. Vitamin K enhanced glucose dependent insulin secretion via the up-regulation of intracellular cAMP. Our results suggested that vitamin K regulates insulin secretion in pancreas.

  25. Effect of exercise for weight control that applied circadian rhythm

    FUJII Hisao, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Sendai University

    2013/04/01 - 2016/03/31

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    The high-fat diet is known to bring obesity. In late years a high-fat diet disturbed the expression of clock-genes in the peripheral organizations such as liver, and it has been reported that it induced to the obesity. Exercise is expected for normalization of this disorder related obesity. In this study, it was intended that examined the influence that a high-fat diet and exercise related to the expression of clock-genes. As a result, exercise improved the weight of high-fat diet-induced obese rat. It was guessed that the effect was affected by the expression of clock-genes related to control of in vivo circadian rhythm.

  26. Correlation analysis of genetic polymorphism of human bitter-taste receptor TAS2R and that of hepatic detoxification enzyme GST

    KOMAI MICHIO, SHIRAKAWA Hitoshi, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2013/04/01 - 2015/03/31

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    Many epidemiological studies have shown that isothiocyanate compounds in the cruciferous plant prevents cancer incidence rate. If the taster of this bitter compounds by TAS2R, bitter taste receptor, the intake of this compound may decrease due to its too much bitterness sensation during eating. Another possibility is hepatic glutathione S-transferase (GST) polymorphism. The latter one is involved in the detoxification mechanism of isothiocyanate compounds after eating in the liver, i.e., we cannot eat cruciferous plants if the GST activity is low due to the enzyme polymorphism. Therefore, we analyzed the relationship of TAS2Rs and GSTs polymorphism in human volunteer, and intended to clarify the mechanism involved in the individual difference of cruciferous plant acceptability. Up to now, we found that the SNP of TAS2R 38 had a close relationship to broccoli bitterness.

  27. Novel funcion of biotin on testosteron production

    HITOSHI Shirakawa, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2013/04/01 - 2015/03/31

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    Biotin, a water soluble vitamin, is essential for four types of carboxylases involved in metabolism of carbohydrate, lipid and amino acids in mammals. We previously explored novel functions of biotin by transcriptome analysis and found that biotin could increase testosterone levels in testis of rats without the enhancement of luteinizing hormone. Here we analyzed the detailed mechanism of enhancement of steroidogenesis by biotin in mouse testis-derived tumor cells. I-10 cells were treated with biotin and the levels of testosterone in cultured medium were measured by ELISA. Biotin significantly increased testosterone levels in time- and dose-dependent manners. This enhancement was abolished by the treatment of inhibitors of adenylate cyclase and protein kinase A. These reuslts indicated that bition stimulates adenylate cyclase in testis derived tumor cells.

  28. Clarification of novel functions of menaquinone-4 converted from vitamin K1 in animal organs

    SHIRAKAWA Hitoshi, KOMAI Michio, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2011/04/01 - 2015/03/31

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    A part of dietary vitamin K is converted to menaquinone-4, one of vitamin K2, in several organs in animals. However, detail of conversion system and function of synthesized menaquinone-4 have not been well elucidated. In this study, we showed that side chain substrate for menaquinone-4 synthesis is the product of mevalonate pathway. And we also showed that menaquinone-4 enhances formation of signaling complex leading to NFkB activation to express anti-inflammation activity. Vitamin K deficient diet enhanced insulin resistance in liver and showed insufficient glucose-induced insulin secretion. These results indicated that vitamin K deficient condition can promote symptom of diabetes in diabetic model animals.

  29. Role of zinc supplementation on improving activity of taste abnormality and anorexia

    KOMAI MICHIO, GOTO Tomoko, SHIMAZAKI Nobuko, SHIRAKAWA Hitoshi, ISONO Kunio, KAMBE Taiho

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2011/04/01 - 2015/03/31

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    We have clarified that carbonic anhydrase, a zinc enzyme, is a key factor to normalize taste abnormality and anorexia. Actually, immunochromatograph measurement of salivary CA 6 (gustin) of the taste abnormal patients showed the lower activity than healthy subjects. After trying to clarify this mechanism, it has been shown that one of the ZnTs transporter may be involved in this mechanism to activate CA and normal taste sensation. These results provided much more adequate and bettter therapy information for human taste disorder by zinc deficiency.

  30. Analysis of glucose-related metabolites as a novel functional component in fruit

    KANAYAMA Yoshinori, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2012/04/01 - 2014/03/31

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    Recently, functional components become important in fruit in addition to size and sweetness. Glucose-realted metabolites that were studied in this project are different from popular functional components such as vitamins and polyphenols. There could be a novel component that is not of antioxidants such as vitamins and polyphenols. In the results obtained in tracer experiments using sea buckthorn, the metabolite was metabolically inactive compared to other sugars. Ripening and environmental stress were investigated because those may affect synthesis and accumulation of the metabolites. The results suggested that the plant was a climacteric type and the accumulation decreased during ripening.

  31. A study on the mechanisms of appetite regulation in super salmon and its application for aquaculture

    NAKANO TOSHIKI, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2011 - 2013

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    Growth in fish is regulated by the growth hormone (GH)-insulin-like growth factor (IGF) axis. Little is known concerning the in vivo levels of global metabolites and the mechanism of enhancement of growth in GH transgenic fish. The present study examined the charged metabolites levels in GH transgenic coho salmon (Oncorhynchus kisutch) by metabolomic analysis.The most notable difference found between transgenic and NT fish was that glycolysis metabolite levels changed in the muscle of transgenic fish. In addition, the change in some metabolite levels in the transgenic fish muscle was enhanced by ration-restriction. However, a few metabolites levels of the TCA cycle were found to decrease in the transgenic fish muscle. These effects observed in muscle were different from effects seen in liver. The results suggest that GH transgenesis can improve the use of carbohydrates as a source of energy associated with rapid growth.

  32. Inter-relationship analysis of genetic polymorphism of human bitter-taste receptor TAS2R and hepatic detoxification enzyme GSTs

    KOMAI MICHIO, SHIRAKAWA Hitoshi, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2011 - 2012

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    Epidemiological studies have shown that isothiocyanate compounds in the cruciferous plant prevents cancer incidence rate. If the taster of this bitter compounds by TAS2R, bitter taste receptor, the intake of this compound may decrease due to its too much bitterness sensation during eating. Another possibility is hepatic glutathione S-transferase (GST) polymorphism. The latter one is involved in the detoxification mechanism of isothiocyanate compounds after eating in the liver, i.e., we cannot eat cruciferous plants if the GST activity is low due to its enzyme polymorphism. Therefore, we analyzed the relationship of TAS2Rs and GSTs polymorphism in human volunteer, and intended to clarify the mechanism involved in the individual difference of cruciferous plant acceptability. Up to now, we found that one of the GST isozyme may be involved in this acceptability, and this may be associated with the non-taster of PTC by TAS2R38, though further detailed study is necessary.

  33. The study of novel regulatory mechanism for the expression of fatty acid synthase gene in re-feeding state of rat liver

    SHIRAKAWA Hitoshi, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2011 - 2012

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    In this study, we tried to identify the novel regulatory mechanism for the gene expression of fatty acid synthase (FASN) which is essential for de novel long chain fatty acid synthesis from acetyl-CoA and malonyl-CoA in re-feeding state of rat liver. The amount of nuclear ChREBP, one of crucial transcription factor for FASN gene, was correlated with FASN mRNA in re-feeding liver. Some miRNA expression that is possible to involved in FASN mRNA expression was enhanced in re-feeding state, suggested that FASN expression may be partly regulated by these miRNA. In case of vagotomy from intestine to brain, operated rats showed enhancement of FASN mRNA expression after re-feeding. These results suggested that afferent nerve is not involved in the enhanced expression of FASN gene after re-feeding.

  34. A study on the mechanisms of growth in super salmon and its application for improvement of muscle production

    NAKANO Toshiki, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2008 - 2010

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    Growth in fish is regulated by the growth hormone (GH)/growth hormone receptor (GHR)/insulin-like growth factor (IGF)-I axis. This GH-IGF-I axis is influenced by several factors. With regard to hormonal effect, it is known that salmon transgenic for GH show increased growth. However, very little is known about the expression patterns of growth-related genes in GH transgenic fish. The present study examined the daily expression patterns of mRNAs for the growth-related genes after feeding in GH transgenic coho salmon (Oncorhynchus kisutch). GH mRNA was detected in both liver and muscle as well as in the pituitary from transgenic fish. GHR mRNA levels in the liver and muscle were higher in transgenic fish than in non-transgenic wild type fish but lower in the pituitary. The expression level of hepatic IGF-I mRNA was greater in transgenic fish. The daily GH, GHR and IGF-I mRNA expression patterns reached their peak at roughly 4-8 h after feeding, however, GHR and IGF-I mRNA expressions in the liver was observed to be irregular in non-transgenic fish. These results suggest that the daily expression patterns for growth-related genes are particularly pronounced in GH transgenic fish. Furthermore, our findings would be useful for consideration of the time of feeding and the optimum time of day for tissue sampling for analysis of growth-related genes in fish.

  35. Clarification of dietary zinc signal transduction through the intestine to the appetite control region of brain.

    KOMAI Michio, SHIRAKAWA Hitoshi, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2008 - 2010

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    Food intake control is a very important factor to keep us healthy condition. We investigated the role of dietary zinc in food intake regulation using rats during early-stage zinc deficiency without decreasing zinc concentrations in plasma and tissues. We found that zinc stimulated food intake after oral but not intraperitoneal administration in Sprague-Dawley rats fed zinc-deficient diet for 3 days. The mRNA expression of neuropeptide Y (NPY) and orexin in the hypothalamus significantly increased 3 hrs after oral but not intraperitoneal administration of zinc. Orally administered zinc may stimulate food intake via orexigenic peptides coupled to the afferent vagus nerve in rats after short-term treatment with a zinc-deficient diet.

  36. Physiological role of vitamin K2 (manaquinone-4) that is generated from other vitamin K analogues in animal organs

    SHIRAKAWA Hitoshi, KOMAI Michio, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2008 - 2010

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    We analyzed the physiological role of de novo synthesized menaquinone-4 (MK-4) in mammal, and also molecular mechanism of anti-inflammation and regulation of steroidogenesis by MK-4.

  37. ヒト苦味・渋味感受性の個人差と遺伝子多型の関係の解析

    駒井 三千夫, 白川 仁, 後藤 知子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的萌芽研究

    Institution: 東北大学

    2008 - 2009

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    これまでの報告では、苦味レセプターTAS2R遺伝子中のSNP(一塩基多型)は苦味感受性に大きな影響を与えていることが判明している。ブロッコリー等のアブラナ科植物の苦味を敏感に感じ取ることが可能な人では、発癌リスクが高いと推定される疫学的データがあるため、その苦味感受性とその物質の代謝酵素の活性も違う可能性も類推される。苦味レセプターの多型と苦味感受性の相関関係を明らかにしていくことは、苦味受容機構の解明につながるほかに、個人の遺伝的素因と疾病発症の関係を解明する糸口になるものと考えられる。よって本研究では、被験者個々人のTAS2R遺伝子のSNP検出と官能検査を行い、苦味感受性に関与するSNPを同定することを目的とした。 今の段階では研究結果の詳細を公開することはできないが、以下に成果の概略を記す。平成21年度の研究では、TAS2R44とTAS2R45におけるSNPの組み合わせに規則性がみられ、これらの遺伝子型はカフェインの閾値とは関連が見られなかったものの、カフェインの苦味強度との関連が見られた。これらのSNPの組み合わせは苦味感受性に影響を及ぼしていることが示唆された。TAS2R44、TAS2R45のハプロタイプを解析した結果、TAS2R44では3つのハプロタイプ、TAS2R45では2つのハプロタイプが観察された。これらのハプロタイプの組み合わせにより、被験者48人は3種類、官能検査を行った38人は2種類の遺伝子型に分類することができた。これらの成果は、今後の研究の進展に極めて重要である。

  38. 糖尿病および心血管疾患を改善する食品中成分のニュートリノジェノミクス解析研究

    白川 仁, ARDIANSYAH, ARDIANSYAH

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 特別研究員奨励費

    Institution: 東北大学

    2007 - 2008

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    我々はこれまでに、米糠のエタノール抽出残渣の糖質分解酵素処理物(DF)がラットにおいて抗酸化、血圧上昇抑制、血漿脂質改善などの生活習慣病を予防、改善する作用を有することを報告してきた。本研究では、昨年度に引き続きDFに含まれている有効成分の化学的性状を明らかにすること、また、同定した成分の作用機構の解明を目的として解析を行った。DFを数段階のカラムクロマトグラフィーによって分離し、トリプトファンを同定した。市販トリプトファンを脳卒中易発性高血圧自然発症ラットSHRSPに単回経口投与し、経時的に収縮期血圧を測定した。その結果、コントロールである蒸留水を投与したラットに比べ、投与1時間から2時間まで有意に血圧が低下した。また、血糖値、血漿インスリン濃度の有意な低下が観察された。これらの結果は、米糠酵素処理物より単離したトリプトファン画分をラットに投与した場合に見られた結果と一致したことから、単離された有効成分がトリプトファンであることが確認された。次に、トリプトファンを長期間(3週間)SHRSPに経口投与した場合の血圧や代謝パラメーターに及ぼす影響について解析を行った。その結果、体重増加、摂食量は両群で影響が見られなかったが、この動物の加齢に伴う血圧上昇がトリプトファン群で有意に低下した。また、血糖値、血漿インスリン濃度の低下、血漿HDLコレステロール濃度の有意な上昇がトリプトファン群で見られた。以上のことから、トリプトファンの長期投与は、SHRSPの糖代謝、脂質代謝異常を改善することが示唆された。

  39. Physiological role of vitamin K2 (manaquinone-4) that is converted from other vitamin K analogue in animal organs

    SHIRAKAWA Hitoshi, KOMAI Michio

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2006 - 2007

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    We analyzed the physiological role of de novo synthesized menaquinone-4 (MK-4) in mammal, and also molecular mechanism of anti-inflammation and regulation of steroidogenesis by vitamin K. I. We developed the model that has low vitamin K in extra-hepatic tissues without any bleeding sym ptom by feeding of dihydrophylloquinone (dK1) as a vitamin K source, and analyzed its phenotype. The plasma osteocalcin level that is one of bone metabolic markers was significantly increased in dK1 feeding group. On the other hand, plasma calcium level was not changed. Therefore dK1 feeding coup d enhance the differentiation of osteoblast not turn over of bone. II. To clarify the direct involvement of testis MK-4 in steroidogenesis, we administered lipopolysaccharide to the subchronic vitamin K deficient rats without any bleeding and analyzed testosterone production in testis. As a result, the synthesis of testosterone and gene expression of Cyp11a was decreased by LPS treatment depending on testis MK-4 concentration. These results indicate that testis MK-4 shows anti-inflammation effect to keep the normal steroidogenesis. III. We analyzed the molecular mechanism of the anti-inflammation by vitamin K using mouse macrophage derived cells. MK-4 significantly reduced IL-1β, IL-6, and TNFα mRNA stimulated by LPS treatment dose-dependent manner. Conditioned medium treated with MK-4 also has a reducing activity of inflammatory cytokine expression. These results suggested that MK-4 metabolite or something secreted from MK-4 treated cells show anti-inflammatory effect.

  40. Study for involvement of lipid glycation in food deterioration and living senescence

    MIYAZAWA Teruo, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2005 - 2007

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    Although Maillard reaction (glycation) between protein and glucose has been thoroughly investigated, we have found that it is possible for glycation to occur between lipid and glucose in food and biological materials. The objective of this research is following; to elucidate whether lipid glycation associate with lipid peroxidation and cellular dysfunction, and to find the food component that able to inhibit lipid glycation. (1) The analysis of alteration of food quality/nutrition value/function by lipid glycation. Processed foods (infant formula, mayonnaise, chocolate) contained a significant amount of Amadori-PEs. As these foods have high amounts of sugar and lipids, lipid glycation would occur during heat processing of these products. Then, various compounds were evaluated for their antiglycative properties using the lipid glycation model system. Pyridoxal 5'-phosphate (PLP) was the most effective antiglycative compounds. PLP could easily be condensed with PE before the glucose/PE reaction occurred. Moreover, oral dose of PLP could effectively prevent the abnormal accumulation of Amadori-PE in the STZ-induced diabetic rats. (2) Ion-trap tandem mass spectrometric analysis of Amadori-glycated phosphatidylethanolamine in human plasma with or without diabetes. We developed an analysis method of Amadori-PE using a quadrupole/linear ion-trap mass spectrometer, the Applied Biosystems QTRAP. Amounts of Amadori-PE in plasma of diabetic patients (0.15 mol% of PE), diabetic patients with chronic hemodialysis (0.29 mol% of PE), and nondiabetic patients with chronic hemodialysis (0.13 mol% of PE) are higher than that of the control group (0.08 mol% of PE). In addition, the concentration of Amadori-PE was proportional to that of phosphatidylcholine hydroperoxide, a reliable indicator of membrane lipid peroxidation, in human plasma (P<0.05). These results indicate that plasma Amadori-PE-glycated lipid product formed under hyperglycemic conditions is an inducer of membrane lipid peroxidation, and therefore lipid glycation plays an active part in the development of human disease.

  41. 苦味および渋味感受性に及ぼす唾液中成分ならびに味覚レセプターの遺伝子多型の影響

    駒井 三千夫, 白川 仁, 後藤 知子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽研究

    Institution: 東北大学

    2005 - 2006

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    近年・苦味・甘味・うま味等の味覚レセプターが同定され、味覚に関して未解明な点を分子レベルで検討することが可能となってきた。苦味の感受性は個人によらて異なっており、例えばアブラナ科植物の苦味を拒否する集団が存在する。疫学的調査では、アブラナ科植物の摂取量が少ない集団での発ガン率が高い結果が出ている。これは、レセプターの感受性の個体差と関連している。本研究は、ヒト被験者の舌の表皮組織及び唾液を非侵襲的に採取して、そのDNAから味覚レセプターを個体ごとに解析して、苦味感受性の個人差を分子レベルで明らかにしようと企図した。併せて、関連性のある味とされる渋味感受性についても、被験者とラットを用いてその渋味の発生する機構を科学的に明らかにすることを目的とした。 1)渋味受容に関する研究 渋味の受容機構をラットの鼓索神経応答から検討した結果、酸性化グリシニンでは唾液中イオン成分が、タンニン酸では唾液中たん白質がそれぞれ渋味の受容に関与していることが推測された。また、酸性化グリシニン溶液では、NaHCO_3溶液の添加量に応じて応答が強くなったことから、酸性化グリシニンの渋味発生機構に唾液由来のNaHCO_3成分が大きく寄与していることが示された。 2)ヒト被験者の苦味レセプター遺伝子SNP(遺伝子多型)解析 本研究により、ヒトDNA調製法、SNP検出法が確立でき、左右の口腔内頬を綿棒でこすることによるサンプリングにより、SNPの検出が可能となった。PROP(プロピルチオウラシル)の感受性がTAS2R38のSNPの組み合わせ、ハプロタイプによって決定されていること、さらに、今回SNPアレルのホモ、ヘテロの組み合わせに規則性があり、集団をタイプ分けすることができた。今回、オーファンレセプターであるTAS2R55のnucleotide位置587、794、875の3つのSNPがカフェインの苦味感受性に関与している可能性が示唆された。

  42. CLARIFICATION OF THE BIOLOGICAL MEANING OF MENAQUINONE-4 SYNTHESIS IN ANIMAL ORGANS

    SHIRAKAWA Hitoshi, KOMAI Michio

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: TOHOKU UNIVERSITY

    2004 - 2005

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    Vitamin K (K) is well known for its role in post-translational activation of a family of nascent proteins to Gla-proteins, such as blood clotting factors and bone Gla-proteins. There are two forms of naturally occurring K: Ki, plant-synthesized phylloquinone; and K2, a family of homologues designated as menaquinone-n (MK-n), which are synthesized by microorganisms including intestinal microflora. However, reports indicate that K analogues are converted into MK-4 in various organs outside the gastrointestinal tract without involvement of bacterial enzymes. Although studies indicate that MK-4 has unique functions related to cell differentiation, induction of apoptosis, and stimulation of transcription of a ligand for the nuclear receptor, these cannot totally explain the physiological significance of MK-4 synthesis in diverse tissues. To help elucidate the biological role of MK-4 production, we used germfree rats to eliminate MK-n synthesized by intestinal flora, and identified patterns of gene expression as a function of K status. Wistar germfree rats were fed either K-deficient, Control (normal level of 1(1), Ki-supplemented, or MK-4-supplemented diets. We obtained testicular gene expression profiles using DNA microarray techniques. Expression of genes involved in cholesterol synthesis and isoprenoid metabolism was down-regulated in the K-deficient group compared with Ki-supplemented animals. Quantitative RT-PCR analysis revealed that testicular MK-4 concentrations were positively correlated with expression of CYP11a, a rate-limiting enzyme involved in testicular testosterone synthesis. Moreover, plasma testosterone concentrations were reduced in K-deficient relative to Control and MK-4-supplemented animals. Together, these results suggest that testicular MK-4 could be a key factor involved in steroid hormone synthesis via regulation of gene expression related to steroidogenesis.

  43. Physiological study on the role of zinc enzyme on the improvement of taste disorders

    KOMAI Michio, SHIRAKAWA Hitoshi, GOTO Tomoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2003 - 2005

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    We have confirmed that NaCl preference is greater in the zinc-deficient and low-zinc rats than in the control (zinc-sufficient and pair-fed) rats after 4 days' feeding. Furthermore, we have also reported that long-term zinc deficiency decreases taste sensitivity at the level of the chorda tympani nerve and that the change in NaCl preference due to zinc deficiency occurs before the decrease in taste sensitivity. In order to clarify the mechanism for the increased NaCl preference observed in zinc-deficient and low-zinc rats at an earlier stage of the feeding, we therefore investigated the effects of zinc deficiency on plasma index (mineral concentration, pH, hematocrit), blood pressure, urinary excretion, water intake and selected hormones. Male 4 week-old Sprague-Dawley rats were divided into three groups (zinc-deficient, low-zinc and pair-fed). At an earlier stage of the feeding period, there was no change of plasma sodium concentration in the zinc-deficient rats. We also investigated that the effects of zinc deficiency on neurohypophysial hormones in rats because brain oxytocin system is important for the regulation of sodium balance via effects on sodium intake and excretion. In consequence, the feeding of zinc-deficient diet causes the decrease of plasma oxytocin concentration even after 4 days' feeding. These results suggest that the dietary signal of zinc-deficiency may reflect NaCl preference, possibly through the hypothalamus-neurohypophysial system.

  44. CLARIFICATION OF THE MECHANISM OF ANIT-DIABETIC EFFET BY THE ADMINISTRATION OF BIOTIN

    SHIRAKAWA Hitoshi, KOMAI Michio

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: TOHOKU UNIVERSITY

    2002 - 2003

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    Biotin is one of water-soluble vitamin that functions as a cofactor of four types of carboxylase involved in lipid, carbohydrate and amino acids metabolism in mammalian. Our group has shown that biotin has a novel function that improves carbohydrate metabolism in diabetes mellitus. This research aimed clarification of mechanism of this novel action of biotin. First of all, we tried to identify site to action of biotin in the stimulation of insulin secretion from the B cells of pancreas. The Langerhan's islet was isolated from rat pancreas, and cultured. Secreted insulin in cultured medium was measured after stimulation of glucose with or without biotin. The secretion of insulin has been increased by biotin administration dose-dependent manner (up to 50μM). This phenomenon was observed when pyruvate was used as a stimulant instead of glucose, therefore biotin was presumed to be participation in the reaction within mitochondria on the glycolytic pathway. Then, the ability of oxidative phosphorylation at the TCA cycle was measured by using radioisotope of glucose with a different labeling site. As a result, the amount of ^<14>CO_2 formations was increased twice by biotin administration when [U-^<14>C] glucose was used as a stimulant, while it was not changed in case of [6-^<14>C] glucose administration. These results indicate that biotin could stimulate ATP synthesis through significant increase of glucose oxidation without the change of rotation ability in TCA cycle. Next, we analyzed the involvement of biotin in the regulation of liver phosphoenolpyruvate carboxykinase (PEPCK) gene expression. PEPCK mRNA was decreased by 40% compared with the control when the biotin was administered to the streptozotocin induced diabetic rat. Therefore biotin has insulin-like action and could improve the condition of diabetic animal. We tried to identify the site of biotin regulation of PEPCK gene using rat hepatoma cell H4IIE that has the insulin susceptibility. PEPCK mRNA increased in H4IIE cells 3 hours after treatment of biotin when cells were incubated with insulin medium. This result indicated that biotin could suppress the insulin action in this cell line.

  45. ビタミン、ミネラルの新しい生理作用の検察―DNAマイクロアレーを用いた解析―

    古川 勇次, 白川 仁, 駒井 三千夫

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽研究

    Institution: 東北大学

    2001 - 2002

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    本研究は、幾つかの栄養状態の異なるモデル動物を用いて、それらの動物における遺伝子の発現変化をDNAマイクロアレイを用いて検出し、その発現パターンをコントロールと比較することによって、栄養素が多岐に渡って遺伝子発現に影響を与えていることを確認するとともに、新規の標的遺伝子を同定し、新しい生理作用を模索することを目的とした。 ビタミンKまたは亜鉛含量の異なる実験食をラットに給餌し、栄養状態の異なるモデル動物を作成した。これらの動物の栄養状態は機器分析法により評価した。ビタミンKの場合、各臓器中のビタミンK含量をHPLCで、亜鉛の場合、血漿亜鉛濃度を原子吸光分光高度計で測定し、それぞれの栄養素の欠乏状態であることを確認した。次に、各臓器からmRNAを精製し、標識ヌクレオチド存在下でcDNAを作製した。得られた標識cDNAと市販DNAマイクロアレイをハイブリダイゼーションさせ、発現プロファイルを得た。 ビタミンK欠乏の場合、肝臓では急性期相タンパク質ファミリーに属する一群の遺伝子の発現が顕著に変化し、このビタミン欠乏によって組織内で炎症反応が起こっていることが示唆された。また、亜鉛欠乏ラットの脳の各部位における発現プロファイルを解析したところ、亜鉛を補因子とする酵素や転写因子の発現変化が見られた。さらに、摂食行動をコントロールするペプチドやシグナル伝達に関与するレセプター、キナーゼなどが変化し、亜鉛欠乏による摂食行動変化を裏付ける結果が得られた。発現量の異なる遺伝子種の幾つかについて、RT-PCR、ノーザンハイブリダイゼーションによってRNA量を定量的に測定したところ、マイクロアレイで得られた結果とほぼ同様の結果が得られたことから、本方法によって実際に発現量の異なる遺伝子種を検出できることが確認された。今後は、栄養素の新規作用に結びつく結果を得るために、多変量解析、階層的クラスタリング法などによって発現プロファイルを詳細に解析する。

  46. Clarification of a novel physiological function of menaquinone-4 (vitamin K2), a postulated active form of vitamin K in various tissues

    KOMAI Michio, ITO Michiko, FURUKAWA Yuji, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2001 - 2002

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    Phylloquinone (vitamin K1=VK1) and the menaquinones (MK-n, or vitamin K2=VK2) are naturally occurring forms of vitamin K. Most of the menaquinones are synthesized by micro-organisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK1 or menadione (=VK3) in the major tissues of germfree rats and mice which lack their intestinal microflora. This result denies Martius' theory that described the participation of bacterial enzyme of the intestinal flora to this conversion. Recently MK-4 has been attracted the attention of researchers due to its specific physiological action such as apoptotic activity on osteoclast cells and leukemia cells, etc. that is beneficial for the maintainance of our healthy quality of life. Therefore, we considered that MK-4 may have a specific novel function in various tissues of animals besides of coagulation in the liver and Gla-protein related action in the other tissues which all analogues of vitamin Ks have. In order to elucidate this hypothesis, we tried to identify genes of which expression is up-or down-regulated under VK deficient condition. DNA microarray technique is a very powerful tool to see the pofile of gene expression simultaneously. Two groups of germfree rats fed VK deficient or VK1 supplemented diet for eight days were sacrificed, and blood and tissue samples were deprived. The results of blood coagulation time (prothrombin time and activated-partial thromboplastin time) and the measurement of VK levels in various tissues supported that rats fed deficient diet showed much more sevefe VK deficient symptoms. The profile of gene expression in the liver, brain, and testis showed that the expression of diverse genes was affected under vitamin K deficiency. The series of genes which were markedly up-regulated in VK deficient liver belonged to a particular group of protein, i.e., acute phase proteins. This result was consistent with our previoous observations that VK deficient germfree mice had acute histological changes in the liver and muscle. Dietary VK1 has an anti-inflammatory effect in the LPS (lipopolysaccharide)-stimulated system in vivo, probably through its conversion to MK-4, because we observed that LPS-stimulated IL-6 expression in the primary cultured spleen was significantly inhibited by the addition of MK-4 to the culture medium rather than VK1. In conclusion, any kind of dietary VK that is considered to convert to MK-4 in various tissues has an anti-inflammatory role in the rodents and probably in humans, though detailed mechanisms involved in the effect of MK-4 should be clarified further.

  47. Clarification of the conversion mechanism of vitamin K analogues to menaquinone-4, a potent hormone-like substance, in the rat tissues.

    KOMAI Michio, ITO Michiko, SHIRAKAWA Hitoshi, FURUKAWA Yuji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    1999 - 2000

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    Menaquinone-4 (MK-4) is one of naturally occurring form of vitmin K_2 (MK-n or K2) which is majorly synthesized in the microorganisms, but recently it has been shown that MK-4 is also synthesized from other vitamin K analogues in various tissues of rat and possibly in other mammalian tissues. According to recent investigations undertaken by us and other American and Dutch researchers, MK-4 abundantly distributes than other VK analogues to various tissues in the rats, such as testis, lung, brain, submandibullar gland, heart, spleen, liver, pancreas, and kidney. Recent results also showed that MK-4 is one of potent accelerator of bone formation in the rats, so MK-4 has been thought to be a potent hormone-like substance. We have newly established an MK-4 formation system in vitro using various tissues of the rats. Substrates for this reaction system are vitamin K_3 (menadione or VK3) or vitamin K_1 (phylloquinone or VK1) as a source for naphthoquinone ring, and geranylgeranyl-diphosphate as a source for isoprenyl side-chain of MK-4, respectively. Supernatant fraction of 900 g of rat kidney homogenate with phophate buffer (pH 7.4) was used as crude enzyme solution. The present experiment undertaken for 2 years revealed that MK-4 production from VK3 was inhibited in a dose-related manner under the presence of warfarin that is an inhibitor for VKs epoxide and VKs reductases. This inhibition was recovered completely by an addition of reducing agent, di-thiothreitol (DTT). This lead us to consider that VK reductase participate in the conversion reaction from VK3 to MK-4, and that VK3-H_2 (reduced form of VK3) and MK-4-H_2 (reduced form of MK-4) might be involved in the reaction pathway as an intermediates. Purification trials of this key enzyme is now going on, and we are observing that the dissociation from the microsomal or mitochondrial membrane fraction made this enzyme much more unstable (less active). We have partly clarified the conversion mechanism of VKs into MK-4 much more clearly than before, and got useful information to purify this enzyme ([MK-4 synthase] as a tentative name). Further investigations are necessary to understand the physiological role of accumulated MK-4 in various tissues in the rat.

  48. The functions and their mechanisms of DNA-binding proteins, HMG1 and HMG2

    YOSHIDA Michiteru, UCHIYAMA Hidefumi, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Science University of Tokyo, Department of Biological Science and Technology

    1997 - 1998

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    (1) The mechanism of DNA-binding of HMG 1/2 proteins and the accompanied changes in DNA conformation : The respective single HMG box in HMG2 protein has DNA-binding activity. The tandem array of the two HMG boxes strengthens the activity. One of the major factor of the stronger DNA-binding activity of box B is resulted from the intercalation of side chain of F107. Computer simulation for HMG2 protein structure showed a structural model in which two boxes are linked in head-to-head manner. The major functional region in HMG2 protein for its preferential binding with supercoiled DNA, DNA unwinding activity, and DNA protection activity from nuclease S1 digestion is in box B flanked by the neighboring sequences. (2) The functions of HMG1/2 proteins : The functional analyses for HMG proteins 1 and 2 revealed that these proteins have multiple functions concerned in transcription, DNA replication, DNA recombination, DNA repair and DNA integration of outer DNA into chromosomal DNA.

  49. 核タンパク質HMG1による転写促進機構の外来遺伝子クロマチンレベルにおける解析

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1997 - 1997

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    1、HMG1中の転写促進領域の同定:HMG1タンパク質の3つのドメインの中で、転写促進に必要な領域はC末端ドメインであることは既に明らかにした。そこでSV40プロモーターの下流にHMG1 cDNA、あるいはC末端ドメインに塩基置換、欠失を施したcDNAを挿入し、レポーター遺伝子と共にCOS-1細胞に導入し、転写促進領域の同定を行った。その結果、C末端の連続した30酸性アミノ酸の最もC末端の5アミノ酸のDDDDEの配列が転写促進に必須であることが明らかになった。さらに、HMG1のC末端ドメイン、HMG2のDNA結合ドメインをもつキメラタンパク質を発現させ、その転写促進能を検索したが、転写促進現象は認められなかった。このことより、酸性C末端部分が分子内の他部位と相互作用して機能していることが示唆された。 2、転写促進においてHMG1、HMG2と共同的に働く因子の検索:HMG1、HMG2によるDNAあるいはクロマチンの構造変化反応において共同的に作用する因子、あるいは構造変化したDNAとHMG1、HMG2との複合体に結合し、転写反応に関与する因子の検索を試みた。培養細胞にHMG1、HMG2発現プラスミドを導入し、一定時間後、細胞核抽出液を調製し、抗HMG抗体をもちいた免疫沈降させた。ここで得られたタンパク質を二次元電気泳動法で解析した。その結果、HMG1、HMG2とそれぞれ特異的に結合して存在する複数種のタンパク質を同定できた。現在、抗HMG1,抗HMG2抗体をリガンドとしたアフィニティークロマトグラフィーによりこれら因子の精製とクローン化を進めている。

  50. HMGタンパク質のDNA結合ドメイン構造と認識機構の解析

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1997 - 1997

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    1,HMG1のDNA結合ドメインのDNA認識機構の解析 HMG1タンパク質のDNA結合に主役的に働くBox Bの中で、DNAへのインターカレーションが予測される101F、102Fの結合における重要性を実験的に明らかにした。さらに分子動力学シミュレーションにより、これらの側鎖の配位と結合との関連を解析した。その結果、Box BのDNAへの結合が102F側鎖のDNAへのインターカレーションにより高められること、この側鎖の方向性を101Fが規定していることが明らかとなった。 2,HMG1、2がもつDNAインテグレーションの促進機能の発見 研究の過程で、HMG1、HMG2が外来遺伝子の宿主ゲノムDNAへの組込み(インテグレーション)を促進する活性を有することを初めて見い出し、促進反応について詳細な検索を行った。HMG1、2を発現するネオマイシン耐性遺伝子を持つプラスミドをHeLa細胞に導入し、G418で選択した。G418耐性コロニー数を計測したところ、コントロールプラスミドを導入の場合と比較して約10倍に増加していた。G418耐性細胞内にインテグレートされたプラスミドのコピー数も約2倍に増加していた。さらに、HMG1、2mRNAに対するアンチセンスRNAをHeLa細胞で発現させるとコロニー数は約1/2に減少した。以上の結果より、HMG1、2が外来遺伝子の宿主ゲノムへのインテグレーションの促進反応に直接関与していることが明らかになった。 3,HMGタンパク質によるDNA依存性プロテインキナーゼ活性促進機構を詳細に解析した。

  51. DNA結合性タンパク質HMG1による転写促進機構のクロマチンレベルにおける解析

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1996 - 1996

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    1.HMG1によるクロマチン構造変化の解析:細胞内に導入したレポーター遺伝子由来のミニクロモソームを分離して、DNaseIに対する高感受性領域を検索したところ、転写促進の見られたHMG1高発現細胞由来のものにおいて高感受性領域が見い出された。現在、この部位の特定を行なっている。 2.HMG1中の転写促進領域の同定:HMG1タンパク質の転写促進領域は、そのC末端領域に存在する酸性アミノ酸の連続配列にあることを明らかにしている。この配列の中で、脊椎動物のHMG1で高度に保存されているDDDDE配列に注目し、塩基置換を施したHMG1変異体を作製し、その転写促進能を比較した。その結果、DDDDQ,DDDNQ変異体では転写促進は見られたが、DDNNQ,DNNNQ,NNNNQでは転写促進は観察されなかった。このことから、HMG1の転写促進にはアスパラギン酸のクラスターが必須であることが明らかとなった。 3.転写促進反応においてHMG1と共同的に働く因子の検索:HMG1による転写促進反応においては、DNAあるいはクロマチンの構造変化を伴うが、この反応においてHMG1と共同的に作用する因子の検索を次の方法により行なった。第一に酵母のTwo hybrid systemをもちいて、HMG1の転写促進に必須な酸性アミノ酸領域と相互作用する因子のスクリーニングを行なった。第二に、HMG1および抗HMG1抗体を固定したカラムを作製し、相互作用する因子の精製を行なった。両方法ともに現在、得られた因子の本体について解析中である。

  52. HMGタンパク質のDNA結合ドメイン構造と認識機構の解析

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1996 - 1996

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    1.HMG2のDNA結合領域の構造解析:HMG2のcDNAよりドメインAB(AとBがリンカーを挟んで連結した配列を大腸菌で高発現させ、均一になるまで精製する系を確立した。この系を用いて、同位体で標識した試料を調製し、現在大阪大学蛋白質研究所など3研究機関の協力のもとNMRによる高次構造解析を進行中である。また、奈良先端技術大学院大学の協力のもとにDNAとの複合体についてX線回折による解析も同時進行中である。 2.部位特異的変異を導入したHMG2のDNA結合領域をもちいた結合機構の解析:立体構造保持(疎水性コアを形成する疎水性アミノ酸)やDNAとの結合(塩基性アミノ酸)、インタカレーションに関与すると期待されるアミノ酸残基を部位特異的変異法により他残基に置換したドメインBを大腸菌で高発現させ、精製した。これら変異体とDNAとの相互作用をゲルシフトアッセイ、表面プラズモン共鳴現象を測定するBIAcore装置によって解析したところ、全ての変異体で結合能の変化と立体構造の差異が観察された。以上の結果より、これらのアミノ酸の構造保持と結合における重要性を明らかにした。 3.示差走査熱量計をもちいたDNA-HMG2複合体の熱安定性の解析:DNAとの複合体の安定性を測定する前段階としてペプチド単独で測定を行なった。その結果、加熱とともにペプチドが凝集し、測定が不可能となった。現在、凝集の原因と考えられるシステイン残基に変異を導入したペプチドを調製し、解析を行なっている。 4.新しいDNA結合タンパク質EPF-5の構造解析:DNA結合機構の解析の一環として、花の組織の特異的発現に関与するZn-Finger型DNA結合性タンパク質EPF-2-5のNMRによる高次構造解析を進行中である。

  53. Studies on DNA-binding, transcriptional stimulation and role in cell proliferation of HMG proteins.

    YOSHIDA Michiteru, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Science University of Tokyo

    1995 - 1996

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    DNA-binding abilities of the various peptides containing DNA-binding domain (s) in HMG1 and 2 proteins were analyzed using gel retardation assay and the measurement of surface plasmon resonance with a BIAcore instrument. The results showed the necessity of both the basic flanking regions of the second DNA-binding domain for strong binding and stabilization of DNA.The mutation of the hydrophobic and basic residues in second HMG1 DNA-binding domain indicated the involvements of the amino acid residues in the formation of hydrophobic core and of complex with DNA.The functional region for DNA-bending and unwinding activities of HMG was also identified by DNA ligation and relaxation assays. The results showed that the second DNA-binding domain and the flanking basic region are important to express the activities. The tertiary structure of DNA-binding domains expressed in E.coli cells and purified in homogeneity is under investigation with NMR and X-ray diffraction. HMG1 stimulates the transcription of the gene in a reporter plasmid. The relations between the transcriptional stimulation and chromatin structure of the reporter gene were analyzed. Minichromosomes derived from the reporter plasmid in HMG1 or HMG2 over-expression cells were digested by DNaseI and microccocal nuclease. Although the respective nucleosomal positions on minichromosomes were not different, the reporter gene in HMG1 over-expression cells was more sensitive to nucleases than that in HMG2 over-expression cells. These results suggested that the transcriptional stimulation by HMG1 may be due to the destabilization of the chromatin structure. The cDNA coding for rat HMG2 was isolated and sequenced. One of anti-sense oligonucleotides designed on the basis of its sequence and transfected into rat 3Y1 cells reduced the cellular level of HMG2 protein. Apparent changes of expression of cellular proteins were observed according to the reduction of the HMG protein.

  54. 転写制御因子HMG1高発現細胞を用いた有用遺伝子高発現系の開発

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1995 - 1995

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    HMG1タンパク質は、高等生物の細胞核に普遍的に存在するDNA結合性タンパク質である。申請者らの研究により、培養細胞内でHMG1を一過性に発現させた場合、共導入したレポーター遺伝子の発現が数倍上昇することを見い出し、この発現上昇はレポーター遺伝子、あるいはプロモーター種に依存しないものであることを認めている。さらに、恒常的にHMG1を高発現する細胞を樹立し、この細胞にレポーター遺伝子を導入した場合、HMG1を一過性に発現させた場合と同様、その発現が数倍上昇した。以上のことから、このHMG1高発現細胞をもちいて、有用遺伝子の高発現系を構築できる可能性が考えられる。本研究では、HMG1の性質を利用して、HMG1高発現細胞内で有用遺伝子高発現系を構築し、その最適化を最終目的とした。当該年度は、HMG1による転写促進領域の同定および改変に関して研究を行なった。 HMG1のC末端側に存在する30残基からなる酸性アミノ酸領域を欠失した変異体を発現するプラスミドをCOS-1細胞にレポーター遺伝子と共に導入した場合、HMG1によるレポーター遺伝子の転写促進能が失われた。また、C末端から5アミノ酸ずつ欠失させたHMG1変異体を発現させ同様に解析した。さらに、HMG2(HMG1との相同性が79%で、酸性アミノ酸の連続配列が23残基からなるタンパク質で、転写促進能を持たない)との対比から、HMG1にユニークな最C末端のDDDDE配列に注目して、この配列のDとEを置換した変異体や酸性アミノ酸領域の21-26の領域を欠失した変異体を発現させ同様に解析した。その結果、全ての変異体で、転写促進は認められなかった。これらの結果より、HMG1による転写促進には、酸性アミノ酸領域全体が必要で、その配列も重要であることが明らかとなった。

  55. HMGタンパク質のDNA結合ドメイン構造と認識機構の解析

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1995 - 1995

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    1、HMG2のDNA結合領域の構造解析:HMG2のcDNAより、DNA結合ドメインAおよびB、さらにAB(AとBがリンカーを挟んで連結した配列)をコードする配列を発現ベクターに挿入し、大腸菌内で高発現させ、均一になるまで精製する系を確立した。現在、この系を用いて標識した試料につき、大阪大学蛋白質研究所など3研究機関の協力のもと、NMRにより高次構造解析を進行中であり、基礎データを順調に蓄積しつつある。引き続き解析を継続する。また、奈良先端技術大学院大学の協力のもとにX線回折による解析も同時に進行中である。 2、表面プラズモン共鳴(SPR)センサ、蛍光測定を用いたHMGタンパク質とDNAとの相互作用の解析:上記の方法でDNA結合ドメインを含む各種配列を高発現、精製した。それらとDNAとの相互作用を、表面プラズモン共鳴現象を測定するBIAcore(Pharmacia)装置を用いて解析をおこない、各DNA結合ドメインに連なる塩基性配列が強い結合と安定性に重要であることを定量的に明かにした。さらに蛍光測定法をもちいた解析より、各芳香族アミノ酸の存在状態を明らかにできた。 3、HMGタンパク質によるDNA bending機構の解析:種々の長さをもつBending,Non-bending型のDNAを作成、これらを用いてHMG中のDNAの折れ曲がり反応の機能ドメインを解析、DNA結合ドメインBとそれに連なる配列が機能領域であることを明らかにした。

  56. HMGタンパク質のDNA結合機構および機能解析研究

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 一般研究(C)

    Institution: 東京理科大学

    1994 - 1994

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    1.HMG2のDNA結合領域の構造解析:HMG2のcDNAより、ドメインA、B、さらにA+Bをコードする領域を発現ベクター(pGEM-EX)のT7プロモーターの下流に挿入し、大腸菌BL21株で高発現させ、均一になるまで精製することに成功した。さらに、一次構造とDNA結合能を有することを確認した。現在、高次構造の解析を大阪大学蛋白質研究所の協力のもとにNMRにより、また奈良技術大学院大学の協力のもとにX線解析により進めている。 2.HMG1の転写促進機構解析系の確立:ウシ・パピローマ・ウイルス遺伝子を持つプラスミド(pBPV)にHMG1、HMG2のcDNAを組み込み、マウス由来のC127細胞へ導入、種々の選択をへてHMG1およびHMG2高発現細胞を得ることに成功した。この細胞に種々のプロモーター、および遺伝子を持つレポータープラスミドを導入しその発現を見たところ、HMG1高発現細胞ではそれらが促進され、またそのクロマチン構造が弛緩していたが、HMG2高発現細胞では促進は見られなかった。これらの結果よりHMG1がクロマチン構造の弛緩を介して転写を促進すること、およびHMG1とHMG2が異なる機能をもつことが明らかとなった。 3.HMG2cDNAに対するアンチセンスRNA発現に伴う細胞周期・増殖の変動:デキサメサゾン誘導によりHMG2cDNAに対するアンチセンスRNAを発現できるプラスミドを構築、ラット繊維芽細胞3Y1へ導入し、ホルモン添加によりHMG2アンチセンスRNAを発現誘導できる細胞株を樹立した。しかし、発現するアンチセンスRNA量が少なく、その後の解析は困難であった。そこで、上記で構築したHMG2高発現細胞をもちいて細胞周期、増殖の制御におけるHMG2タンパク質の役割解析を進めている。

  57. HMGタンパク質のDNA結合ドメイン構造と認識機構の解析

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1994 - 1994

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    〔1〕HMG1およびHMG2単独DNA結合領域の構造解析:HMG1,HMG2のcDNAのうち、それぞれのドメインAおよびドメインBをコードする領域を発現ベクター(pGEM-EX)のT7プロモーターの下流に挿入し、大腸菌BL21株で高発現させ、均一になるまで精製することに成功した。さらに、一次構造とDNA結合能を有することを確認した。現在、高次構造の解析を大阪大学蛋白質研究所の協力のもとにNMRにより、また奈良技術大学院大学の協力のもとにX線解析により進めている。 〔2〕DNA結合領域、ドメインA+Bの構造解析:HMG1,HMG2のcDNAより、ドメインA+Bをコードする領域を同様に発現ベクターに挿入し、大腸菌で高発現させ、均一になるまで精製することに成功した。さらに、一次構造とDNA結合能を有することを確認した。今後、上記の解析結果を参考にしながら、高次構造の解析を大阪大学蛋白質研究所の協力のもとにNMRにより、また奈良技術大学院大学の協力のもとにX線解析により進める予定である。 〔3〕表面プラズモン共鳴技術(BIAcore System)を用いたDNA結合領域とDNAとの相互作用の解析:上記のDNA結合領域A,B,A+Bに加えてそれらを結ぶリンカー(l)をもつAl,Bl,AlBlを同様に調製した。これらとDNAとの相互作用をBIAcore Systemを用いて検索した。その結果、リンカー領域がHMG1,HMG2の立体構造保持と結合強化に重要であり、また結合が多段階反応であることが明らかとなった。

  58. 転写調節因子HMG2の癌遺伝子産物による転写促進機構の解析

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1993 - 1993

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    高等動物に普遍的に存在する核タンパク質HMG2は、DNAの高次構造を識別して結合、転写反応を調節する因子であることがこれまでの我々の研究より示唆されている。ラット繊維芽細胞3Y1の細胞周期における変動を解析したところ、G2/M期において、またアデノウイルスE1A、E1Bのトランスフォームにより、HMG2の発現が促進されていることが明らかとなった。一方、HMG2遺伝子の転写制御領域の解析より、この遺伝子発現には、転写開始点上流-621から-492の遺伝子領域が必要であり、この領域中の-499から-485の配列に結合する約85kDaの新しい転写因子(HMG2TF)の存在を確認した。そこで、HMG2遺伝子の転写制御領域をもちいて、HMG2のトランスフォームによる発現促進機構を解明することを目的とした。ヒトHMG2遺伝子5′-上流領域をクロラムフェニコール・アセチルトランスフェラーゼ遺伝子の上流に接続(CATプラスミド)し、ヒトHeLa細胞および293細胞にトランスフエクトし、HMG2プロモーター活性に対するE1A、E1Bの影響を解析した。その結果、いずれの細胞でも、E1A、E1Bの影響を受けるDNA領域は認められなかった。しかし、HMG2TFの結合量は2〜3倍増加し、HMG2遺伝子の転写量の増加(約4倍)と正の相関が認められた。以上の結果より、アデノウイルスE1A、E1BのトランスフォームによるHMG2の発現上昇は、HMG2TFの制御領域への結合量の増加によるものと推定された。

  59. HMGboxのDNA結合機構および転写反応における役割の研究

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 一般研究(C)

    Institution: 東京理科大学

    1993 - 1993

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    高等動植物の細胞核に存在する核タンパク質HMG1およびHMG2(以下HMG1/2と略)は、DNA結合性である。そのDNA結合モチーフ(HMG-box)は、多くの転写因子に存在し、そのDNA認識と結合の機構、転写における係わりあいが注目されつつある。本研究では、HMG-boxを高発現、精製後、高次構造を明らかにし、HMG-boxのDNAの認識と結合機構について解明することを目的とした。HMG1/2に2つずつ含まれるHMG-box(ドメインA、ドメインB)をコードするcDNAを発現プラスミドに挿入し、T7システムをもちいて大腸菌内で高発現させた。菌体より、各HMG-boxを均一になるまで精製し、現在大阪大学蛋白質研究所の協力のもと、NMRによる高次構造解析を行なっている。次に、各HMG-boxとDNAとの結合機構について、ゲルシフトアッセイをもちいて解析した。その結果、各ドメイン単独ではDNA結合性は持つものの、HMG1/2で認められるDNA高次構造に対する優先的結合、および協同的結合性は認められなかった。また、DNAの巻戻し活性を調べたところ、各HMG-boxでは、ほとんど活性が認められなかったが、両HMG-boxをもつ構成物では巻戻し活性が認められた。以上のことから、HMG1/2の2つのHMG-boxは、DNA結合性を持つが、DNA構造に対する特異性および強力な結合性を示すには、両HMG-boxがタンデムに結合していることが必要であることが示唆された。

  60. 転写調節因子HMGZの癌遺伝子産物による発現促進機構の解析

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1992 - 1992

  61. STUDIES ON TRANSCRIPTION PROGRESSION FACTORS AND THE APPLICATION

    YOSHIDA Michiteru, SHIRAKAWA Hitoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for General Scientific Research (C)

    Institution: SCIENCE UNIVERSITY OF TOKYO, DEPARTMENT OF BIOLOGICAL SCIENCE AND TECHNOLOGY

    1991 - 1992

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    (1) The binding of HMG1 and HMG2 with DNA : The binding of HMG1/2 proteins with plasmid DNA of various conformations was examined. The results indicated that HMG1/2 preferentially bind to negatively supercoiled DNA recognizing the conformation without sequence spcificity, and change the DNA topology. The cooperative binding of HMG1/2 to the unusual-structured DNA under torsional stress may, thus, remove the transcriptional block by dissolving the structure. The two DNA binding domains in the HMG protein molecule were over-expressed in E. coil system. The tertiary structures of the purified domains are under investigation. (2) Expression of HNG1 and HMG2 genes dependent on the cell cycle and growth : The expression levels of HMG1/2 genes during cell cycle and growth were analyzed. The results showed that HMG2 gene expression is enhanced at G2 phase in the cell cycle and depending on the cell proliferation, in contrast with HMG1 gene. The relative amount of HMG proteins in the nuclei correlated with the expression level of the respective genes. (3) HMG1 protein stimulates in vivo transcription : The effect of HMG1 gene expression in cells co-transfected with a reporter gene was investigated. The results showed that HMG1 protein stimulates the transcriptional activity of the gene co-transfected. The in vivo system may be useful for the effective production of functionally-active proteins.

  62. 核蛋白質による十字型DNA構造の特異的識別・結合の様式および同構造解消の機構

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1990 - 1992

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    1.HMG box、およびDNAとHMG boxとの複合体の立体構造解析:HMG2のcDNAよりDNA結合領域“HMG box"A,BおよびA+BをコードするcDNAをTクプロモーターをもつプラスミドpGEMに組み込み、大腸菌の中で単独分子として、それぞれ高発現できる系を確立した。高発現したポリペプチドをそれぞれ分離精製する方法を見いだした。現在、多量の試料を調製中であり、引きつづき大阪大学との共同研究により、結晶化とX線回折、およびNMPによる立体構造解析を行なう。 2、HMG boxとDNAとの結合様式の解明:HMG boxとDNAとの結合を解析するためのゲルシフトアッセイ条件を設定した。この系でHMG2のHMG boxBとプラミドDNAとの結合と測定したところ、超らせん型、弛緩型、直鎖型のいずれのDNA型にも同程度の結合を示し、また超らせん型DNAへの結合の程度はHMG2に比較して弱かった。これらの結果から、HNG2の超らせん型DNAに対する強い、優先的結合にはHMG boxA,Bの2つが相揃い、その相互作用が必須であることが示された。 3、転写反応におけるHMG boxの影響解析:動物培養細胞COS-1における外来遺伝子の発現活性によりHMG1の効果を検定したところ、HMG1の発現に伴い、外来遺伝子の発現が数倍増加した。さらに、この発現上昇は転写段階での促進によることが明らかになった。一方、HMG1の変異タンパク質を構築し、その発現に対する影響を検索した結果、HNG boxA+Bのみではレポータ遺伝子の発現が抑えられた。この結果、HMG boxはDNA結合活性を有するのみであり、HMG1分子のC末端の酸性アミノ酸領域が転写領域が転写促進の機能をドメインであることが明りかとなった。

  63. DNA結合性タンパク質HMGIによる培養細胞への外来遺伝子導入・発現の効率化

    白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東京理科大学

    1991 - 1991

  64. 核タンパク質による十字型DNA構造の特異的識別・結合の様式および同構造解消の機構

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1990 - 1991

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    1.HMG1,HMG2の一次構造上のDNA結合部位の同定:HMG1タンパク質を化学および酵素分解後、ペプチドを分離し、DNA結合能を測定した。この結果と一次構造、および最近見いだされたHMGタンパク質類似のDNA結合ドメインをもつタンパク質との比較により、結合に必要な2つの領域をほぼ特定できた。 2.HMG1とHMG2のDNAへの親和性の差異の検索:前年度の研究によりゲルシフト・アッセイでHMG1,2の間にDNA結合能の大きな差異が認められた。この差異がリン酸化に由来するか否かを検索する為、脱リン酸化処理を行い、DNA結合能を比較したところ変化は認められなかった。他の結果と併せて考えると、DNA結合能の差異は両タンパク質の修飾によるのではなく、一次構造に起因するものと推定される。 3.DNAとHMG2複合体の立体構造:HMG2タンパク質の上記2つの結合領域のうち、ドメインAをコ-ドするcDNAの塩基配列をPーガラクトシダ-ゼのcDNAの下流への連結し、P_Rプロモ-タ-をもつプラスミドへ挿入、大腸菌ヘトランスフォ-ムした。誘導によって高発現した融合タンパク質を分離精製後、ドメインAを酵素分解により切出し、分離精製する系を確立できた。今後、NMRおよびX線結晶回析を行い、DNA結合領域の立体構造解析を進める。 4.HMG2遺伝子構造と発現制御領域の検索:ヒトHMG2遺伝子の単離にはじめて成功し、全塩基配列を決定した。この遺伝子の発現に必要な上流配列を特定し、その領域に結合する核内因子の存在を認め、結合配列を決定した。その発現促進の機構を検索中である。

  65. 核蛋白質による十字型DNA構造の特異的識別・結合の様式および同構造解消の機構

    吉田 充輝, 白川 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 重点領域研究

    Institution: 東京理科大学

    1990 - 1990

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    1.(1)DNAに対するHMG1,HMG2(HMGと略)タンパク質の結合の度合を測定するために、ゲルシフト・アッセイ法の条件を設定した。 (2)この系を用いて解析の結果、HMGはI型DNAに最も親和性が高く、Ir、II型の共存下では、I型がほぼ飽和するとIr型,II型へも結合した。III型とI型DNA共存下では、まずI型に優先的に結合した。III型DNAに結合しているHMGも後にI型DNAを加えると、I型DNAへ移行した。 (3)十字型構造をとり1本鎖ル-プを持つものと、持たないものとの2種類の合成DNAをもちいて解析の結果より、HMGは1本鎖グル-プ構造により高い親和性を持つことが明らかとなった。 (4)これらの結果から、HMGは塩基配列には依存せず、1本鎖領域を認識結合した後、2本本鎖部分へ協同的に結合するものと推察される。 2.一次構造上相同性が高いHMG1とHMG2についてDNAへの結合の度合は大きく異なることがゲルシフト・アッセイの結果で明らかとなり、異なる機能をもつことも考えられる。 3.HMG1タンパク質のプロテア-ゼ,あるいはBrCN分解断片とDNAとの相互作用の解析から,HMG1のDNA結合領域のひとつは、N末端より74番目のアミノ酸までの領域にあることが確かめられた。 4.DNAとHMGとの結合構造を解析する為に、DNA結合ドメインを高発現させる条件を設定しつつある。HMGのDNA認識・結合の様式は従来のそれらとは全く異なる新しいモチ-フであることが予想され、新知見を得ることができるものと考えられる。 5.HMG2の遺伝子領域(約5Kbp)をクロ-ニングし、その全塩基配列をはじめて明らかにし、新しい知見が得られた。この結果は、今後の研究に重要な基盤を与える。

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Social Activities 1

  1. 平成17年度食科学フォーラム

    2006/01/18 -

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    秋田県総合食品研究所主催の平成17年度食科学フォーラムにおいて、「ビタミンの新規作用の検索」と題して、講演を行った。

Media Coverage 1

  1. 米ぬかに血圧・コレステロール下げる効果

    読売新聞

    2006/03/10

    Type: Newspaper, magazine

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  1. 米糠に含まれる生活習慣病を予防する新規成分の同定とその高度利用に関する研究

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    米糠エタノール抽出残渣を酵素処理して得られた成分が高血圧症を発症するモデル動物であるSHRSPの血圧上昇を抑制し、腎機能マーカー、血漿脂質組成を改善する作用を有することを見出した。本研究では、その有効成分を分離、精製し、その化学構造を明らかにして、米糠に更なる機能性を付加する。

  2. 米糠に含まれる生活習慣病を予防する新規成分の同定とその高度利用に関する研究

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    米糠エタノール抽出残渣を酵素処理して得られた成分が高血圧症を発症するモデル動物であるSHRSPの血圧上昇を抑制し、腎機能マーカー、血漿脂質組成を改善する作用を有することを見出した。本研究では、その有効成分を分離、精製し、その化学構造を明らかにして、米糠に更なる機能性を付加する。

  3. 米糠廃棄物の再資源化を目指した新規機能性成分の単離とその応用

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    米糠エタノール抽出残渣を酵素処理して得られた成分が高血圧症を発症するモデル動物であるSHRSPの血圧上昇を抑制し、腎機能マーカー、血漿脂質組成を改善する作用を有することを見出した。本研究では、その有効成分を分離、精製し、その化学構造を明らかにして、米糠に更なる機能性を付加する。

  4. 大豆たん白質の渋味発生機構に関する電気生理学的研究

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    大豆たん白質の渋味は、サポニンなどの不純物により誘起されているという考えや、タンパク質そのものに渋味を誘起する作用があるという考えがあることから、この発生機構を電気生理学的手法と神経生理学的手法により明らかにする。

  5. 2’3’-ジヒドロフィロキノンを用いた生体内変換型ビタミンKの生理的役割に関する研究

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    ビタミンK1誘導体（ジヒドロフィロキノン）をラットに与え、メナキノン-4低下による影響を解析する。

  6. 雑穀類の摂取による糖代謝ならびに脂質改善作用に関する研究

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    生理機能活性のある雑穀類を食品中に入れて有効利用する試みは、各方面で行われているが、その作用機構などは不明な部分が多い。本研究では、雑穀類の機能性の作用機構を解明し、生活習慣病予防への有効利用を視野にして研究を行う。

  7. 米糠成分による生活習慣病予防

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    米糠に含まれる、血圧上昇抑制、血糖値上昇抑制成分をラットを用いて分離同定し、その作用機序について解析を行う。

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