Details of the Researcher

PHOTO

Ryuta Tobe
Section
Graduate School of Agricultural Science
Job title
Associate Professor
Degree

  • 博士（農学）（京都大学）

  • 修士（農学）（東北大学）

Research History 6

  • 2022/04 - Present
    Tohoku University　Graduate School of Agricultural Science

  • 2020/04 - 2022/03
    NIPRO corporation

  • 2019/04 - 2020/03
    Ritsumeikan University　Department of Biotechnology, College of Llife Science

  • 2015/04/01 - 2018/03/31
    Ritsumeikan University　Department of Biotechnology, College of Llife Science

  • 2009/07 - 2015/03
    National Institutes of Health　National Cancer Institute　Postdoctoral fellow

  • 2009/04/01 - 2009/06/30
    Kyoto University　Institute for Chemical Research, Division of Environmental Chemistry

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Education 3

  • Kyoto University　Graduate School of Agriculture　Division of Applied Biosciences

    - 2009/03

  • Tohoku University　Graduate School of Agricultural Science　Division of Bioscience and Biotechnology for Future Bioindustries

    - 2006/03

  • Tohoku University　Faculty of Agriculture　Department of Applied Bio-Sciences

    - 2004/03

Professional Memberships 3

  • 日本畜産学会

    2022/04 - Present

  • 日本微量元素学会

    2015/04 - Present

  • "Japan Society for Bioscience, Biotechnology, and Agrochemistry "

    2009/04 - Present

Research Interests 1

  • Selenium, Selenoproteins, Microorganisms, Mammals, Enzymes, Metabolism, Cancer

Research Areas 3

  • Life sciences / Applied microbiology /

  • Life sciences / Cell biology /

  • Life sciences / Molecular biology /

Awards 6

  1. 奨励賞

    2018/07　日本微量元素学会

  2. 若手海外優秀発表賞

    2018/06　日本ビタミン学会

  3. 若手奨励賞

    2017/04　立命館大学生命科学部

  4. 優秀口頭発表賞

    2016/07　日本微量元素学会

  5. 海外ポスドク招聘賞

    2013/12　日本分子生物学会

  6. Travel award

    2010/05　International Symposium on Selenium in Biology and Medicine

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Papers 37

  1. Identification of Genes Associated with Resistance to Persulcatusin, a Tick Defensin from Ixodes persulcatus. International-journal Peer-reviewed

    So Shimoda, Junya Ito, Tasuke Ando, Ryuta Tobe, Kiyotaka Nakagawa, Hiroshi Yoneyama

    Microorganisms　12　(2)　2024/02/19

    DOI： 10.3390/microorganisms12020412 　

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    Antimicrobial peptides (AMPs) are present in a wide range of plants, animals, and microorganisms. Since AMPs are characterized by their effectiveness against emergent antibiotic-resistant bacteria, they are attracting attention as next-generation antimicrobial compounds that could solve the problem of drug-resistant bacteria. Persulcatusin (IP), an antibacterial peptide derived from the hard tick Ixodes persulcatus, shows high antibacterial activity against various Gram- positive bacteria as well as multidrug-resistant bacteria. However, reports on the antibacterial action and resistance mechanisms of IP are scarce. In this study, we spontaneously generated mutants showing increased a minimum inhibitory concentration (MIC) of IP and analyzed their cross-resistance to other AMPs and antibiotics. We also used fluorescent probes to investigate the target of IP activity by evaluating IP-induced damage to the bacterial cytoplasmic membrane. Our findings suggest that the antimicrobial activity of IP on bacterial cytoplasmic membranes occurs via a mechanism of action different from that of known AMPs. Furthermore, we screened for mutants with high susceptibility to IP using a transposon mutant library and identified 16 genes involved in IP resistance. Our results indicate that IP, like other AMPs, depolarizes the bacterial cytoplasmic membrane, but it may also alter membrane structure and inhibit cell-wall synthesis.

  2. Identification of four genes responsible for antimicrobial resistance of MEL-B against S. aureus Peer-reviewed

    Shinya Yamauchi, So Shimoda, Akio Kawahara, Tomohiro Sugahara, Shuhei Yamamoto, Masao Kitabayashi, Atsushi Sogabe, Christine A. Jansen, Ryuta Tobe, Ryota Hirakawa, Jahidul Islam, Mutsumi Furukawa, Hiroshi Yoneyama, Tomonori Nochi

    Biochemical and Biophysical Research Communications　149566-149566　2024/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2024.149566 　

    ISSN： 0006-291X

  3. l-Alanine Exporter AlaE Functions as One of the d-Alanine Exporters in Escherichia coli Peer-reviewed

    Satoshi Katsube, Keiichiro Sakai, Tasuke Ando, Ryuta Tobe, Hiroshi Yoneyama

    International Journal of Molecular Sciences　2023/06/16

    DOI： 10.3390/ijms241210242 　

  4. Characterization of Staphylococcus aureus Isolates from Bovine Mastitis and Bulk Tank Milk: First Isolation of Methicillin-Susceptible Staphylococcus aureus in Japan. International-journal Peer-reviewed

    Ryota Miyazawa, So Shimoda, Keiichi Matsuda, Ryuta Tobe, Tasuke Ando, Hiroshi Yoneyama

    Microorganisms　10　(11)　2022/10/26

    DOI： 10.3390/microorganisms10112117 　

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    Staphylococcus aureus is one of the most important pathogens in humans as well as in livestock. Particularly, bovine mastitis caused by S. aureus is a serious issue in dairy farms due to disease recurrence. Here, cases of S. aureus-mediated intramammary infection occurring in the Miyagi Prefecture in Japan were monitored from May 2015 to August 2019; a total of 59 strains (49 from bovine milk and 10 from bulk milk) were obtained from 15 dairy farms and analyzed via sequence-based typing methods and antibiotic susceptibility tests. Two pairs of isolates were determined as recurrence cases from the same cows in distinct farms. The sequence type (ST), spa type, and coa type of each pair were the same: one pair showed ST705, t529, and VIb and the other showed ST352, t267, and VIc. In addition, the possession of toxin genes analyzed of each pair was exactly the same. Furthermore, seven oxacillin-sensitive clonal complex 398 isolates were obtained from a single farm. This is the first confirmed case of a Methicillin-Sensitive SA (MSSA) ST398 strain isolated from mastitis-containing cows in Japan. Our findings suggest that nationwide surveillance of the distribution of ST398 strains in dairy farms is important for managing human and animal health.

  5. Group II truncated haemoglobin YjbI prevents reactive oxygen species-induced protein aggregation in Bacillus subtilis. International-journal Peer-reviewed

    Takeshi Imai, Ryuta Tobe, Koji Honda, Mai Tanaka, Jun Kawamoto, Hisaaki Mihara

    eLife　11　2022/09/20

    DOI： 10.7554/eLife.70467 　

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    Oxidative stress-mediated formation of protein hydroperoxides can induce irreversible fragmentation of the peptide backbone and accumulation of cross-linked protein aggregates, leading to cellular toxicity, dysfunction, and death. However, how bacteria protect themselves from damages caused by protein hydroperoxidation is unknown. Here, we show that YjbI, a group II truncated haemoglobin from Bacillus subtilis, prevents oxidative aggregation of cell-surface proteins by its protein hydroperoxide peroxidase-like activity, which removes hydroperoxide groups from oxidised proteins. Disruption of the yjbI gene in B. subtilis lowered biofilm water repellence, which associated with the cross-linked aggregation of the biofilm matrix protein TasA. YjbI was localised to the cell surface or the biofilm matrix, and the sensitivity of planktonically grown cells to generators of reactive oxygen species was significantly increased upon yjbI disruption, suggesting that YjbI pleiotropically protects labile cell-surface proteins from oxidative damage. YjbI removed hydroperoxide residues from the model oxidised protein substrate bovine serum albumin and biofilm component TasA, preventing oxidative aggregation in vitro. Furthermore, the replacement of Tyr63 near the haem of YjbI with phenylalanine resulted in the loss of its protein peroxidase-like activity, and the mutant gene failed to rescue biofilm water repellency and resistance to oxidative stress induced by hypochlorous acid in the yjbI-deficient strain. These findings provide new insights into the role of truncated haemoglobin and the importance of hydroperoxide removal from proteins in the survival of aerobic bacteria.

  6. Initial step of selenite reduction via thioredoxin for bacterial selenoprotein biosynthesis International-journal Peer-reviewed

    Atsuki Shimizu, Ryuta Tobe, Riku Aono, Masao Inoue, Satoru Hagita, Kaito Kiriyama, Yosuke Toyotake, Takuya Ogawa, Tatsuo Kurihara, Kei Goto, N. Tejo Prakash, Hisaaki Mihara

    International Journal of Molecular Sciences　22　(20)　2021/10/02

    DOI： 10.3390/ijms222010965 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  7. Complete Genome Sequence of Pseudomonas stutzeri Strain F2a, Isolated from Seleniferous Soil. International-journal Peer-reviewed

    Masao Inoue, Yuu Hirose, Ryuta Tobe, Shigeki Saito, Riku Aono, N Tejo Prakash, Hisaaki Mihara

    Microbiology resource announcements　10　(33)　e0063121　2021/08/19

    DOI： 10.1128/MRA.00631-21 　

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    Pseudomonas stutzeri is a potential candidate for bioremediation of selenium-contaminated grounds and waters. Here, we report the complete genome sequence of a novel strain, F2a, which was isolated from a seleniferous area of Punjab, India. The genome sequence provides insight into the potential selenium oxyanion-reducing activity of this strain.

  8. Genetic analysis of tellurate reduction reveals the selenate/tellurate reductase genes ynfEF and the transcriptional regulation of moeA by NsrR in Escherichia coli. International-journal Peer-reviewed

    Daiki Fujita, Ryuta Tobe, Hirotaka Tajima, Yukari Anma, Ryo Nishida, Hisaaki Mihara

    Journal of biochemistry　169　(4)　477-484　2021/04/29

    DOI： 10.1093/jb/mvaa120 　

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    Several bacteria can reduce tellurate into the less toxic elemental tellurium, but the genes responsible for this process have not yet been identified. In this study, we screened the Keio collection of single-gene knockouts of Escherichia coli responsible for decreased tellurate reduction and found that deletions of 29 genes, including those for molybdenum cofactor (Moco) biosynthesis, iron-sulphur biosynthesis, and the twin-arginine translocation pathway resulted in decreased tellurate reduction. Among the gene knockouts, deletions of nsrR, moeA, yjbB, ynbA, ydaS and yidH affected tellurate reduction more severely than those of other genes. Based on our findings, we determined that the ynfEF genes, which code for the components of the selenate reductase YnfEFGH, are responsible for tellurate reduction. Assays of several molybdoenzymes in the knockouts suggested that nsrR, yjbB, ynbA, ydaS and yidH are essential for the activities of molybdoenzymes in E. coli. Furthermore, we found that the nitric oxide sensor NsrR positively regulated the transcription of the Moco biosynthesis gene moeA. These findings provided new insights into the complexity and regulation of Moco biosynthesis in E. coli.

  9. Characterization of a novel class of glyoxylate reductase belonging to the β-hydroxyacid dehydrogenase family in Acetobacter aceti International-journal Peer-reviewed

    Jakkaphan Kumsab, Ryuta Tobe, Tatsuo Kurihara, Yuu Hirose, Taketo Omori, Hisaaki Mihara

    Bioscience, Biotechnology, and Biochemistry　84　(11)　2303-2310　2020/11/01

    Publisher: Informa UK Limited

    DOI： 10.1080/09168451.2020.1797470 　

    ISSN： 0916-8451

    eISSN： 1347-6947

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    Enzymes related to β-hydroxyacid dehydrogenases/3-hydroxyisobutyrate dehydrogenases are ubiquitous, but most of them have not been characterized. An uncharacterized protein with moderate sequence similarities to Gluconobacter oxydans succinic semialdehyde reductase and plant glyoxylate reductases/succinic semialdehyde reductases was found in the genome of Acetobacter aceti JCM20276. The corresponding gene was cloned and expressed in Escherichia coli. The gene product was purified and identified as a glyoxylate reductase that exclusively catalyzed the NAD(P)H-dependent reduction of glyoxylate to glycolate. The strict substrate specificity of this enzyme to glyoxylate, the diverged sequence motifs for its binding sites with cofactors and substrates, and its phylogenetic relationship to homologous enzymes suggested that this enzyme represents a novel class of enzymes in the β-hydroxyacid dehydrogenase family. This study may provide an important clue to clarify the metabolism of glyoxylate in bacteria. Abbreviations: GR: glyoxylate reductase; GRHPR: glyoxylate reductase/hydroxypyruvate reductase; HIBADH: 3-hydroxyisobutyrate dehydrogenase; SSA: succinic semialdehyde; SSAR: succinic semialdehyde reductase.

  10. Complete Genome Sequence of an Acetic Acid Bacterium, Acetobacter aceti JCM20276. International-journal Peer-reviewed

    Yuu Hirose, Jakkaphan Kumsab, Ryuta Tobe, Hisaaki Mihara

    Microbiology resource announcements　9　(42)　2020/10/15

    DOI： 10.1128/MRA.00962-20 　

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    Acetobacter aceti is used in industry to produce vinegar by converting ethanol into acetic acid. We determined the complete genome sequence of A aceti JCM20276, which is composed of one chromosome and four plasmids. This study may contribute to a better understanding of the genes necessary for acetic acid production.

  11. Selenite uptake by outer membrane porin ExtI and its involvement in the subcellular localization of rhodanese-like lipoprotein ExtH in Geobacter sulfurreducens International-journal Peer-reviewed

    Jahan MI, Juengwiwattanakitti P, Izu Y, Tobe R, Imai T, Mihara H

    Biochemical and Biophysical Research Communications　516　(2)　474-479-479　2019/08

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2019.06.037 　

    ISSN： 0006-291X

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    Selenite reduction is a key step in the biogeochemical cycle of selenium-an essential trace element for life. A variety of bacteria can transform selenite into elemental selenium nanoparticles on the cell surface via anaerobic respiration or detoxification processes. However, the proteins associated with the uptake of selenite for these processes are poorly understood. In this study, we investigated the role of an outer membrane porin-like protein, ExtI, in selenite permeation in Geobacter sulfurreducens. We demonstrated that selenite uptake and selenium nanoparticle formation were impaired in an extI-deficient strain. A putative rhodanese-like lipoprotein is encoded by an extH gene located immediately upstream of extI in the genome. We showed that ExtH is translocated into inner and outer membranes and that extI deficiency exclusively affects the localization of ExtH in the outer membrane. Coelution of ExtI and ExtH during gel filtration analysis of the outer membrane fraction of wild-type cells suggests a direct protein-protein interaction between them. Taken together, these results lead us to propose a physiological role for ExtI as a selenite channel associated with ExtH in the outer membrane.

  12. Partial purification and characterization of glyoxylate dehydrogenase from Acetobacter aceti JCM20276 Peer-reviewed

    Jakkaphan K, Tobe R, Mihara H

    Trace Nutrients Research　in press　2019

  13. Comparative Biochemical Characterization of L-Asparaginases from Four Species of Lactic Acid Bacteria Peer-reviewed

    Phetsri K, Furukawa M, Yamashiro R, Kawamura Y, Hayashi J, Tobe R, Toyotake Y, Wakayama M

    Journal of Biotechnology and Biomedicine　in press　(03)　2019

    Publisher: Fortune Journals

    DOI： 10.26502/jbb.2642-91280015 　

    eISSN： 2642-9128

  14. Characterization of a novel porin-like protein, ExtI, from geobacter sulfurreducens and its implication in the reduction of selenite and tellurite International-journal Peer-reviewed

    Mst. Ishrat Jahan, Ryuta Tobe, Hisaaki Mihara

    International Journal of Molecular Sciences　19　(3)　E809　2018/03/11

    Publisher: MDPI AG

    DOI： 10.3390/ijms19030809 　

    ISSN： 1422-0067 1661-6596

  15. Radioactive 75Se labeling and detection of selenoproteins International-journal Peer-reviewed

    Sun Hee Yim, Ryuta Tobe, Anton A. Turanov, Bradley A. Carlson

    Methods in Molecular Biology　1661　177-192　2018

    Publisher: Humana Press Inc.

    DOI： 10.1007/978-1-4939-7258-6_13 　

    ISSN： 1064-3745

  16. Delivery of selenium to selenophosphate synthetase for selenoprotein biosynthesis International-journal Peer-reviewed

    Ryuta Tobe, Hisaaki Mihara

    Biochimica et Biophysica Acta - General Subjects　1862　(11)　2433-2440-2440　2018

    Publisher: Elsevier B.V.

    DOI： 10.1016/j.bbagen.2018.05.023 　

    ISSN： 1872-8006 0304-4165

  17. Identification of selenomethionine, selenocysteine, and Se-methylselenocysteine in the selenium-enriched common ice plant Peer-reviewed

    Tobe R, Koga H, Tani Y, Tajima H, Tsuji A, Mihara H

    Biomed Res Trace Elements　28　135-142　2017/12

    DOI： 10.11299/brte.28.135 　

    ISSN： 1880-1404

  18. Relationship between the glycosphingolipids and phospholipids synthesis and the mycelial growth in Neurospora crassa Peer-reviewed

    Tobe R, Tani Y, Kataoka M, Yamashita Y, Mihara H

    Trace Nutrients Research　33　13-20　2016/12

    ISSN： 1346-2334

  19. Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration International-journal Peer-reviewed

    Bradley A. Carlson, Ryuta Tobe, Elena Yefremova, Petra A. Tsuji, Victoria J. Hoffmann, Ulrich Schweizer, Vadim N. Gladyshev, Dolph L. Hatfield, Marcus Conrad

    REDOX BIOLOGY　9　(9)　22-31　2016/10

    DOI： 10.1016/j.redox.2016.05.003 　

    ISSN： 2213-2317

  20. Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals International-journal Peer-reviewed

    Ryuta Tobe, Bradley A. Carlson, Jang Hoe Huh, Nadia P. Castro, Xue-Ming Xu, Petra A. Tsuji, Sang-Goo Lee, Jeyoung Bang, Ji-Woon Na, Young-Yun Kong, Daniel Beaglehole, Eileen Southon, Harold Seifried, Lino Tessarollo, David S. Salomon, Ulrich Schweizer, Vadim N. Gladyshev, Dolph L. Hatfield, Byeong Jae Lee

    BIOCHEMICAL JOURNAL　473　(14)　2141-2154　2016/07

    DOI： 10.1042/BCJ20160393 　

    ISSN： 0264-6021

    eISSN： 1470-8728

  21. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis International-journal Peer-reviewed

    Erik Schoenmakers, Bradley Carlson, Maura Agostini, Carla Moran, Odelia Rajanayagam, Elena Bochukova, Ryuta Tobe, Rachel Peat, Evelien Gevers, Francesco Muntoni, Pascale Guicheney, Nadia Schoenmakers, Sadaf Farooqi, Greta Lyons, Dolph Hatfield, Krishna Chatterjee

    JOURNAL OF CLINICAL INVESTIGATION　126　(3)　992-996　2016/03

    DOI： 10.1172/JCI84747 　

    ISSN： 0021-9738

    eISSN： 1558-8238

  22. Mechanism, structure, and biological role of selenocysteine lyase Peer-reviewed

    Hisaaki Mihara, Ryuta Tobe, Nobuyoshi Esaki

    Selenium: Its Molecular Biology and Role in Human Health, Fourth Edition　113-123　2016/01/01

    Publisher: Springer International Publishing

    DOI： 10.1007/978-3-319-41283-2_10 　

  23. Selenocysteine tRNA [Ser]Sec: From nonsense suppressor tRNA to the quintessential constituent in selenoprotein biosynthesis Peer-reviewed

    Bradley A. Carlson, Byeong Jae Lee, Petra A. Tsuji, Ryuta Tobe, Jin Mo Park, Ulrich Schweizer, Vadim N. Gladyshev, Dolph L. Hatfield

    Selenium: Its Molecular Biology and Role in Human Health, Fourth Edition　3-12　2016/01/01

    Publisher: Springer International Publishing

    DOI： 10.1007/978-3-319-41283-2_1 　

  24. A non-radioactive assay for selenophosphate synthetase activity using recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8 International-journal Peer-reviewed

    Saho Kamada, Takahiro Okugochi, Kaori Asano, Ryuta Tobe, Hisaaki Mihara, Michiko Nemoto, Kenji Inagaki, Takashi Tamura

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　80　(10)　1970-1972　2016

    DOI： 10.1080/09168451.2016.1200458 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  25. Differences in Redox Regulatory Systems in Human Lung and Liver Tumors Suggest Different Avenues for Therapy International-journal Peer-reviewed

    Ryuta Tobe, Bradley A. Carlson, Petra A. Tsuji, Byeong Jae Lee, Vadim N. Gladyshev, Dolph L. Hatfield

    CANCERS　7　(4)　2262-2276　2015/12

    DOI： 10.3390/cancers7040889 　

    ISSN： 2072-6694

  26. Cell Proliferation and Motility are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells. International-journal Peer-reviewed

    Bang J, Huh JH, Na JW, Lu Q, Carlson BA, Tobe R, Tsuji PA, Gladyshev VN, Hatfield DL, Lee BJ

    Mol Cells　38　(5)　457-65-65　2015/05

    DOI： 10.14348/molcells.2015.0007 　

    ISSN： 1097-2765

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    The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.

  27. Deficiency of the 15-kDa selenoprotein led to cytoskeleton remodeling and non-apoptotic membrane blebbing through a RhoA/ROCK pathway International-journal Peer-reviewed

    Jeyoung Bang, Mihyun Jang, Jang Hoe Huh, Ji-Woon Na, Myoungsup Shim, Bradley A. Carlson, Ryuta Tobe, Petra A. Tsuji, Vadim N. Gladyshev, Dolph L. Hatfield, Byeong Jae Lee

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　456　(4)　884-890　2015/01

    DOI： 10.1016/j.bbrc.2014.12.059 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  28. Regulation of HIF-1α activity by overexpression of thioredoxin is independent of thioredoxin reductase status. International-journal Peer-reviewed

    Naranjo-Suarez S, Carlson BA, Tobe R, Yoo MH, Tsuji PA, Gladyshev VN, Hatfield DL

    Mol Cells.　36　(2)　151-7-7　2013/08

    DOI： 10.1007/s10059-013-0121-y 　

    ISSN： 1097-2765

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    Under hypoxic conditions, cells activate a transcriptional response mainly driven by hypoxia-inducible factors (HIFs). HIF-1α stabilization and activity are known to be regulated by thioredoxin 1 (Txn1), but how the thioredoxin system regulates the hypoxic response is unknown. By examining the effects of Txn1 overexpression on HIF-1α function in HeLa, HT-29, MCF-7 and EMT6 cell lines, we found that this oxidoreductase did not stabilize HIF-1α, yet could increase its activity. These effects were dependent on the redox function of Txn1. However, Txn1 deficiency did not affect HIF-1α hypoxic-stabilization and activity, and overexpression of thioredoxin reductase 1 (TR1), the natural Txn1 reductase, had no influence on HIF-1α activity. Moreover, overexpression of Txn1 in TR1 deficient HeLa and EMT6 cells was still able to increase HIF-1α hypoxic activity. These results indicate that Txn1 is not essential for HIF-1α hypoxic stabilization or activity, that its overexpression can increase HIF-1α hypoxic activity, and that this effect is observed regardless of TR1 status. Thus, regulation of HIF-1α by the thioredoxin system depends on the specific levels of this system's major components.

  29. High error rates in selenocysteine insertion in mammalian cells treated with the antibiotic doxycycline, chloramphenicol, or geneticin. International-journal Peer-reviewed

    Tobe R, Naranjo-Suarez S, Anton, Carlson BA, Robert, Tsuji PA, Yoo MH, Gladyshev VN, Hatfield DL

    J Biol Chem.　288　(21)　14709-15-15　2013/05

    DOI： 10.1074/jbc.M112.446666 　

    ISSN： 0021-9258

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    Antibiotics target bacteria by interfering with essential processes such as translation, but their effects on translation in mammalian cells are less well characterized. We found that doxycycline, chloramphenicol, and Geneticin (G418) interfered with insertion of selenocysteine (Sec), which is encoded by the stop codon, UGA, into selenoproteins in murine EMT6 cells. Treatment of EMT6 cells with these antibiotics reduced enzymatic activities and Sec insertion into thioredoxin reductase 1 (TR1) and glutathione peroxidase 1 (GPx1). However, these proteins were differentially affected due to varying errors in Sec insertion at UGA. In the presence of doxycycline, chloramphenicol, or G418, the Sec-containing form of TR1 decreased, whereas the arginine-containing and truncated forms of this protein increased. We also detected antibiotic-specific misinsertion of cysteine and tryptophan. Furthermore, misinsertion of arginine in place of Sec was commonly observed in GPx1 and glutathione peroxidase 4. TR1 was the most affected and GPx1 was the least affected by these translation errors. These observations were consistent with the differential use of two Sec tRNA isoforms and their distinct roles in supporting accuracy of Sec insertion into selenoproteins. The data reveal widespread errors in inserting Sec into proteins and in dysregulation of selenoprotein expression and function upon antibiotic treatment.

  30. Mammalian Trit1 is a tRNA([Ser]Sec)-isopentenyl transferase required for full selenoprotein expression International-journal Peer-reviewed

    Noelia Fradejas, Bradley A. Carlson, Eddy Rijntjes, Niels-Peter Becker, Ryuta Tobe, Ulrich Schweizer

    BIOCHEMICAL JOURNAL　450　(2)　427-432　2013/03

    DOI： 10.1042/BJ20121713 　

    ISSN： 0264-6021

  31. Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis International-journal Peer-reviewed

    Bradley A. Carlson, Min-Hyuk Yoo, Ryuta Tobe, Charles Mueller, Salvador Naranjo-Suarez, Victoria J. Hoffmann, Vadim N. Gladyshev, Dolph L. Hatfield

    CARCINOGENESIS　33　(9)　1806-1813　2012/09

    DOI： 10.1093/carcin/bgs230 　

    ISSN： 0143-3334

  32. Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via a thioredoxin-independent mechanism International-journal Peer-reviewed

    Ryuta Tobe, Min-Hyuk Yoo, Noelia Fradejas, Bradley A. Carlson, Soledad Calvo, Vadim N. Gladyshev, Dolph L. Hatfield

    BIOCHEMICAL JOURNAL　445　(3)　423-430　2012/08

    DOI： 10.1042/BJ20120618 　

    ISSN： 0264-6021

  33. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth International-journal Peer-reviewed

    Petra A. Tsuji, Salvador Naranjo-Suarez, Bradley A. Carlson, Ryuta Tobe, Min-Hyuk Yoo, Cindy D. Davis

    NUTRIENTS　3　(9)　805-817　2011/09

    DOI： 10.3390/nu3090805 　

    ISSN： 2072-6643

  34. Inducible L-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli International-journal Peer-reviewed

    Hatsuhiro Hori, Hiroshi Yoneyama, Ryuta Tobe, Tasuke Ando, Emiko Isogai, Ryoichi Katsumata

    APPLIED AND ENVIRONMENTAL MICROBIOLOGY　77　(12)　4027-4034　2011/06

    DOI： 10.1128/AEM.00003-11 　

    ISSN： 0099-2240

  35. Specific transfer of selenium in selenoprotein biosynthesis Peer-reviewed

    Tobe R, Mihara H, Kurihara T, Esaki N

    Biomed. Res. Trace Elements,　21　(4)　187-193　2010/09

    ISSN： 0916-717X

  36. Identification of Proteins Interacting with Selenocysteine Lyase International-journal Peer-reviewed

    Ryuta Tobe, Hisaaki Mihara, Tatsuo Kurihara, Nobuyoshi Esaki

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　73　(5)　1230-1232　2009/05

    DOI： 10.1271/bbb.90065 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  37. Characterization of Human Selenocysteine Synthase Involved in Selenoprotein Biosynthesis Peer-reviewed

    Abe K, Mihara H, Tobe R, Esaki N

    Biomed. Res. Trace Elements.　19　(1)　80-83　2008

    ISSN： 0916-717X

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Misc. 4

  1. 必須微量元素セレンの生理作用と代謝 セレンタンパク質の機能とセレン代謝

    戸部隆太, 三原久明

    化学と生物　57　(6)　2019

    ISSN： 0453-073X

  2. 鉄硫黄クラスターおよびセレンタンパク質生合成とその分子機構

    戸部隆太, 三原久明

    硫酸と工業　70　(2)　2017

    ISSN： 0370-8047

  3. セレンも世界を救う

    戸部隆太

    生物工学会誌　94　(7)　2016

    ISSN： 0919-3758

  4. 抗生物質が引き起こす哺乳動物細胞セレンタンパク質生合成異常「セレンって何?」から,「セレンってなんだか面白そう!」への変化に期待を込めて

    戸部隆太

    化学と生物　52　(4)　2014

    ISSN： 0453-073X

Books and Other Publications 7

  1. Selenium in plants; Bacteria versus Selenium: A View from the Inside Out

    Staicu LC, Oremland RS, Tobe R, Mihara H

    Springer　2017

    ISBN: 9783319562483

  2. Selenium; Selenocysteine tRNA[Ser]Sec: From Nonsense Suppressor tRNA to the Quintessential Constituent in Selenoprotein Biosynthesis

    Carlson BA, Lee BJ, Tsuji PA, Tobe R, Park JM, Schweizer U, Gladyshev VN, Hatfield DL

    Springer　2016

    ISBN: 9781461410256

  3. Selenium; Mechanism, Structure, and Biological Role of Selenocysteine Lyase

    Mihara H, Tobe R, Esaki N

    Springer　2016

    ISBN: 9781461410256

  4. Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals; Selenium and Cancer

    Hatfield DL, Carlson BA, Tsuji PA, Tobe R, Gladyshev VN

    Academic Press　2016

    ISBN: 9780128021682

  5. Diversity of Selenium Functions in Health and Disease; Selenocysteine tRNA[Ser]Sec: The Central Component of Selenoprotein Biosynthesis

    Carlson BA, Tobe R, Tsuji PA, Yoo MH, Feigenbaum L, Tessarollo L, Lee BJ, Schweizer U, Gladyshev VN, Hatfield DL

    CRC Press　2015

    ISBN: 9781482251265

  6. Selenium; Mouse models that target removal or over-expression of the selenocysteine tRNA[Ser]Sec gene to elucidate the role of selenoproteins in health and development

    Carlson BA, Yoo MH, Xu XM, Tsuji P, Tobe R, Naranjo-Suarez S, Cheng F, Feigenbaum L, Tesserrollo L, Gladyshev VN, Hatfield DL

    Springer　2011

    ISBN: 9781461410256

  7. Selenium; Selenoproteins harboring a split personality in both preventing and promoting cancer

    Yoo MH, Carlson BA, Tsuji PA, Tobe R, Naranjo-Suarez S, Lee BJ, Davis CD, Gladyshev VN, Hatfield DL

    Springer　2011

    ISBN: 9781461410256

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Presentations 45

  1. Molecular biological analysis of antimicrobial peptides against pathogenic bacteria Invited

    International Symposium on Designing Foods for the Future　2024/09/19

  2. 乳房炎罹患牛から単離した黄色ブドウ球菌の性状および分子解析

    東北畜産学会　2023/08/29

  3. Function and structure of multiheme-containing selenoprotein Invited

    International Selenium Conference　2019/11/21

  4. タンパク質の工学的創製と高活性セレンタンパク質 Invited

    日本毒性学会 生体金属部会主催 メタルバイオサイエンス研究会2019　2019/10/29

  5. Geobacter sulfurreducens のマルチヘムセレンタンパク質型亜セレン酸還元酵素の機能・構造解析

    第５回 日本セレン研究会　2019/07/21

  6. 細菌および動植物におけるセレンの代謝とセレンタンパク質の解析

    日本微量元素学会　2019/07/07

  7. Bacillus sp. NTP-1 株の新奇 dimethyl sulfoxide reductase family 酵素の機能解析

    日本微量栄養素学会　2019/06/22

  8. Bacillus属細菌におけるテルル酸還元酵素の解析

    メタルバイオサイエンス研究会2018　2018/11/17

  9. Functional analysis of thioredoxin in selenium delivery in bacteria

    The 7th International Selenium Conference (Se 2018)　2018/10/03

  10. Geobacter sulfurreducens の新規ポリン様タンパク質の機能解析

    第91回日本生化学会　2018/09/24

  11. Reduction of toxic chalcogen oxyanions, selenite and tellurate, by Bacillus sp. NTP-1 isolated from a seleniferous soil

    Extremophiles 2018　2018/09/19

  12. カルコゲンオキシアニオン還元菌 Bacillus sp. NTP-1 株におけるテルル酸還元酵素の解析

    酵素補酵素研究会　2018/09/12

  13. 細菌のセレンタンパク質生合成とそのセレン源供給メカニズムの解明

    第4回日本セレン研究会　2018/07/21

  14. Geobacter sulfurreducens 由来の新規ポリン様タンパク質 ExtI の解析

    第29回日本微量元素学会　2018/07/07

  15. Geobacter sulfurreducens 由来の新奇マルチヘム含有セレンタンパク質の解析

    日本農芸化学会2018年度大会　2018/03/16

  16. 細菌におけるテルル酸還元機構の解析

    特殊環境微生物セミナー2017　2017/10/06

  17. Cellulomonas sp. D3a 株におけるカルコゲンオキシアニオン還元機構の解析

    環境微生物系学会合同大会　2017/08/30

  18. Delivery of selenide to selenophosphate synthetase for selenoprotein biosynthesis in bacteria

    The 11th International Symposium on Selenium in Biology and Medicine (Se 2017)　2017/08/14

  19. 細菌におけるセレン化合物の代謝とセレンタンパク質生合成 Invited

    日本微量元素学会　2017/07/29

  20. Geobacter sulfurreducens 由来の新規マルチヘム含有セレンタンパク質MHSEPの解析

    酵素補酵素研究会　2017/06/23

  21. Pseudomonas putida の D-リジン異化代謝における制御機構の解析

    日本ビタミン学会　2017/06/09

  22. 微生物におけるセレンおよびテルルの代謝

    第３回日本セレン研究会　2017/05/27

  23. Geobacter sulfurreducens が有するマルチヘム含有セレンタンパク質の精製と機能解析

    日本農芸化学会　2017/03/18

  24. Selenium Delivery System for Selenophosphate Synthetase in Bacteria

    The 6th International Selenium Conference (Se 2016)　2016/10/22

  25. グラム陽性菌Clostridium sticklandii 由来D-セレノシスチンα,β-リアーゼに関する研究

    日本農芸化学会関西支部例会　2016/09/17

  26. Purification and characterization of D-cysteine desulfhydrase from Gram-positive bacterium Clostridium sticklandii

    The Fifth International Conference on Cofactors & Active Enzyme Molecule 2016　2016/09/05

  27. Identification of a novel selenium-supplying factor in selenoprotein biosynthesis

    日本微量元素学会　2016/07/31

  28. セレン強化植物およびセレン耐性微生物に含まれるセレン種のスペシエーション分析

    日本微量栄養素学会　2016/06/25

  29. 細菌におけるセレノリン酸合成酵素への基質供給系の解析

    日本ビタミン学会　2016/06/18

  30. Characterization and Genome Analysis of Cellulomonas sp. D3a, a Selenium and Tellurium Oxyanions-Reducing Bacterium

    The International Conference on the Chemistry of Selenium and Tellurium (ICCST-13)　2016/05/24

  31. Removal of Glutathione Peroxidase 4 in Mouse Liver Leads to Early Lethality and Vitamin E Can Compensate for Its Loss.

    Experimental Biology 2016　2016/04/03

  32. セレノリン酸合成酵素の基質供給系の解析

    酵素補酵素研究会　2015/07

  33. Defferences in redox regulatory systems in human liver and lung cancers suggest different avenues for therapy

    Trace Elements in Man and Animals (TEMA15)　2014/06/26

  34. 哺乳類細胞において抗生物質が引き起こすセレノシステイン挿入異常

    日本分子生物学会　2013/12

  35. The antibiotics, doxycycline (Dox), chloramphenicol (Cp) and geneticin (G418), cause high error rates in selenocysteine (Sec) insertion in mammalian cells

    The 10th International Symposium on Selenium in Biology and Medicine (Selenium 2013)　2013/09

  36. Antibiotics induce mistranslation of selenocysteine residue in selenoproteins

    ASBMB Annual Meeting　2012/04

  37. Increased Selenite Cytotoxicity in a Cancer Cell Line: Thioredoxin Reductase 1 Assumes New Roles in Cancer

    ASBMB Annual Meeting　2011/04

  38. Increased Sodium Selenite Cytotoxicity in Thioredoxin Reductase 1 Knockdown Cancer Cells

    The 9th International Symposium on Selenium in Biology and Medicine (Selenium 2010)　2010/05

  39. 亜セレン酸代謝におけるセレン結合型チオレドキシンの解析

    日本ビタミン学会　2009/05

  40. セレノシステインリアーゼに相互作用するタンパク質の解析

    日本微量元素学会　2008/07

  41. Streptococcus bovis におけるNADPH 生合成系の解析

    日本農芸化学会　2008/03

  42. セレン代謝におけるセレノシステインリアーゼ結合タンパク質の機能解析

    日本分子生物学会 日本生化学会　2007/12

  43. ヒトSLA/LP の精製と解析

    日本微量元素学会　2007/07

  44. Streptococcus bovis における外来遺伝子発現のコドン使用頻度の影響

    日本農芸化学会　2006/03

  45. 嫌気性細菌由来のα-ケトグルタル酸遺伝子クラスターの形質導入によるグルタミン酸生産菌の開発

    日本農芸化学会　2005/03

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Research Projects 6

  1. 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

  2. 生理活性ペプチドおよび抗菌タンパク質を用いた家畜感染症に対する新規防除戦略の構築

    米山 裕, 戸部 隆太, 伊藤 幸博, 榎本 賢

    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

    2022/04/01 - 2025/03/31

  3. セレン耐性菌を用いたセレン代謝機構の解明

    戸部 隆太

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 立命館大学

    2019/04/01 - 2020/03/31

    More details Close

    セレン (Se) は、ヒトをはじめ多くの生物にとって必須微量元素の１つであり、ヒトでは不足しても過剰にあっても重大な障害ももたらす。その代謝経路を解明するため欧米を中心に活発な研究が進んでいるが、全容解明には遠い段階にある。本研究では、Se 代謝の特性が異なる 3 種の Se 耐性細菌（Pseudomonas sp. F2a 株、Bacillus sp. NTP-1 株、Cellulomonas sp. D3a 株）を実験モデルとして、生物における Se 代謝メカニズムの解明を目指した。これらの菌株は、大腸菌や近縁菌よりもはるかに優れた Se オキシアニオン耐性能・還元能を有し、余剰 Se オキシアニオンを Se ナノ粒子として細胞外に排出する。これら菌株の全ゲノム配列を解読し、解析した結果、F2a株のみがセレンタンパク質合成系（同化能）を有することが推測された。一方、NTP-1株およびD3a株は、ゲノム上にセレンタンパク質合成系の遺伝子を持たず、Se オキシアニオンの異化的還元能のみを有すると考えられた。 Cellulomonas sp. D3a 株の亜セレン酸還元特性を解析した結果、好気下では、富栄養培地および最少培地のいずれにおいても、本菌の生育は亜セレン酸の添加により著しく阻害された。しかし、嫌気下では、富栄養培地においては高い亜セレン酸耐性能および還元能を示し、最少培地では亜セレン酸の添加濃度依存的な生育が認められた。一方で、亜セレン酸と化学的に類似するオキシアニオンを最少培地にそれぞれ添加した場合では、本菌の生育は認められなかった。このことより、本菌はグルコースを基質、亜セレン酸を最終電子受容体とする亜セレン酸呼吸システムを有することが示唆された。本菌の亜セレン酸還元酵素を同定するために、ランダム変異を導入し、亜セレン酸還元能欠損株を複数獲得した。

  4. Development and application of expression system for active selenoproteins

    Mihara Hisaaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)

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

    Institution: Ritsumeikan University

    2018/06/29 - 2020/03/31

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    Selenoproteins are expected to be useful in industries. Selenoproteins contains a selenocysteine residue in their active sites. Because there are several differences in the mechanisms of selenoprotein biosynthesis among Eukarya, Bacteria, and Archaea, microbial overproduction of heterologous selenoproteins has not been established. In this study, we constructed a luciferase-based reporter assay system that is useful for exploring SECISs that function in Escherichia coli. We examined the function of 9 SECIS structure from 9 selenoproteins genes from an obligately anaerobic bacterium using this reporter assay system in E. coli. We showed that 5 SECIS among 9 can be used as functional SECISs in E. coli.

  5. Reactions specific to active selenium species in selenoprotein biosynthesis

    Mihara Hisaaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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

    Institution: Ritsumeikan University

    2016/04/01 - 2019/03/31

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    We identified the chemical structure of active selenium that was formed on the active site of thioredoxin as an intermediate in the process prior to the supply of selenium substrate to selenophosphate synthetase, which is required for selenoprotein biosynthesis. We also found a novel selenite reductase that has a selenocysteine residue and five c-type heme in a dissimilatory metal-reducing bacterium Geobacter sulfurreducens. The enzymatic properties of the selenoprotein was investigated. In addition, we showed that a gene encoding the novel selenite reductase is involved in the formation of elemental selenium on the surface of the bacterial cells.

  6. Analysis of selenium metabolism utilizing high concentration selenium-resistant bacteria

    Tobe Ryuta, MIHARA Hisaaki, HIROSE Yuu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Ritsumeikan University

    2016/04/01 - 2018/03/31

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    The selenium-resistant bacterium Pseudomonas sp. F2a was isolated from a soil around the selenium accumulation area in India, and its whole genome sequence was revealed using a next-generation sequencer. Based on the genomic information, the genes that may be involved in selenium resistance or selenium reduction ability were identified. Some of the identified genes were cloned and analyzed as purified proteins. In addition, the intermediate of selenite and the reductant protein was analyzed by MS.

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Teaching Experience 7

  1. Animal microbiology　Tohoku University

  2. 微生物生理学　立命館大学

  3. タンパク質工学　立命館大学

  4. 生物工学基礎演習2　立命館大学

  5. 顕微鏡観察基礎実験　立命館大学

  6. 生化学実験２　立命館大学

  7. 生化学実験１　立命館大学

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