研究者詳細

顔写真

サイトウ　サカエ
齋藤　さかえ
Sakae Saito
所属
高等研究機構未来型医療創成センター　研究部
職名
講師
学位

  • 理学 （大阪大学）

研究分野 1

  • ライフサイエンス / 分子生物学 /

論文 11

  1. Functional Characterization of 40 CYP3A4 Variants by Assessing Midazolam 1′-Hydroxylation and Testosterone 6β-Hydroxylation 国際誌 査読有り

    Masaki Kumondai, Evelyn Marie Gutiérrez Rico, Eiji Hishinuma, Akiko Ueda, Sakae Saito, Daisuke Saigusa, Shu Tadaka, Kengo Kinoshita, Tomoki Nakayoshi, Akifumi Oda, Ai Abe, Masamitsu Maekawa, Nariyasu Mano, Noriyasu Hirasawa, Masahiro Hiratsuka

    Drug Metabolism and Disposition　49　(3)　212-220　2021年3月

    出版者・発行元： American Society for Pharmacology & Experimental Therapeutics (ASPET)

    DOI： 10.1124/dmd.120.000261 　

    ISSN：0090-9556

    eISSN：1521-009X

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    CYP3A4 is among the most abundant liver and intestinal drug-metabolizing cytochrome P450 enzymes, contributing to the metabolism of more than 30% of clinically used drugs. Therefore, interindividual variability in CYP3A4 activity is a frequent cause of reduced drug efficacy and adverse effects. In this study, we characterized wild-type CYP3A4 and 40 CYP3A4 variants, including 11 new variants, detected among 4773 Japanese individuals by assessing CYP3A4 enzymatic activities for two representative substrates (midazolam and testosterone). The reduced carbon monoxide-difference spectra of wild-type CYP3A4 and 31 CYP3A4 variants produced with our established mammalian cell expression system were determined by measuring the increase in maximum absorption at 450 nm after carbon monoxide treatment. The kinetic parameters of midazolam and testosterone hydroxylation by wild-type CYP3A4 and 29 CYP3A4 variants (K m , k cat , and catalytic efficiency) were determined, and the causes of their kinetic differences were evaluated by three-dimensional structural modeling. Our findings offer insight into the mechanism underlying interindividual differences in CYP3A4-dependent drug metabolism. Moreover, our results provide guidance for improving drug administration protocols by considering the information on CYP3A4 genetic polymorphisms. SIGNIFICANCE STATEMENT: CYP3A4 metabolizes more than 30% of clinically used drugs. Interindividual differences in drug efficacy and adverse-effect rates have been linked to ethnicity-specific differences in CYP3A4 gene variants in Asian populations, including Japanese individuals, indicating the presence of CYP3A4 polymorphisms resulting in the increased expression of loss-of-function variants. This study detected alterations in CYP3A4 activity due to amino acid substitutions by assessing the enzymatic activities of coding variants for two representative CYP3A4 substrates.

  2. Impacts of NRF2 activation in non–small‐cell lung cancer cell lines on extracellular metabolites 査読有り

    Daisuke Saigusa, Ikuko N. Motoike, Sakae Saito, Michael Zorzi, Yuichi Aoki, Hiroshi Kitamura, Mikiko Suzuki, Fumiki Katsuoka, Hirofumi Ishii, Kengo Kinoshita, Hozumi Motohashi, Masayuki Yamamoto

    Cancer Science　111　(2)　667-678　2020年2月

    出版者・発行元： Wiley

    DOI： 10.1111/cas.14278 　

    ISSN：1347-9032

    eISSN：1349-7006

  3. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome 査読有り

    Shu Tadaka, Fumiki Katsuoka, Masao Ueki, Kaname Kojima, Satoshi Makino, Sakae Saito, Akihito Otsuki, Chinatsu Gocho, Mika Sakurai-Yageta, Inaho Danjoh, Ikuko N. Motoike, Yumi Yamaguchi-Kabata, Matsuyuki Shirota, Seizo Koshiba, Masao Nagasaki, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Atsushi Shimizu, Jun Yasuda, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    Human Genome Variation　6　(1)　2019年12月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s41439-019-0059-5 　

    eISSN：2054-345X

  4. Identification of genetic alterations in extramammary Paget disease using whole exome analysis 国際誌 査読有り

    Yukiko Kiniwa, Jun Yasuda, Sakae Saito, Rumiko Saito, Ikuko N. Motoike, Inaho Danjoh, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto, Ryuhei Okuyama

    Journal of Dermatological Science　94　(1)　229-235　2019年4月

    DOI： 10.1016/j.jdermsci.2019.03.006 　

    ISSN：0923-1811

    eISSN：1873-569X

  5. Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare 査読有り

    Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

    The Journal of Biochemistry　165　(2)　139-158　2019年2月1日

    出版者・発行元： Oxford University Press (OUP)

    DOI： 10.1093/jb/mvy096 　

    ISSN：0021-924X

    eISSN：1756-2651

  6. Functional Characterization of 21 Allelic Variants of Dihydropyrimidine Dehydrogenase Identified in 1070 Japanese Individuals 査読有り

    Eiji Hishinuma, Yoko Narita, Sakae Saito, Masamitsu Maekawa, Fumika Akai, Yuya Nakanishi, Jun Yasuda, Masao Nagasaki, Masayuki Yamamoto, Hiroaki Yamaguchi, Nariyasu Mano, Noriyasu Hirasawa, Masahiro Hiratsuka

    Drug Metabolism and Disposition　46　(8)　1083-1090　2018年8月

    出版者・発行元： American Society for Pharmacology & Experimental Therapeutics (ASPET)

    DOI： 10.1124/dmd.118.081737 　

    ISSN：0090-9556

    eISSN：1521-009X

  7. Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals 査読有り

    Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N. Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

    Journal of Human Genetics　63　(2)　213-230　2018年2月

    DOI： 10.1038/s10038-017-0347-1 　

    ISSN：1434-5161

    eISSN：1435-232X

  8. Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing 査読有り

    Yusuke Shibuya, Hideki Tokunaga, Sakae Saito, Kazurou Shimokawa, Fumiki Katsuoka, Li Bin, Kaname Kojima, Masao Nagasaki, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda

    GENES CHROMOSOMES & CANCER　57　(2)　51-60　2018年2月

    DOI： 10.1002/gcc.22507 　

    ISSN：1045-2257

    eISSN：1098-2264

  9. Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing 査読有り

    Xiaoqing Pan, Naoki Nariai, Noriko Fukuhara, Sakae Saito, Yukuto Sato, Fumiki Katsuoka, Kaname Kojima, Yoko Kuroki, Inaho Danjoh, Rumiko Saito, Shin Hasegawa, Yoko Okitsu, Aiko Kondo, Yasushi Onishi, Fuji Nagami, Hideyasu Kiyomoto, Atsushi Hozawa, Nobuo Fuse, Masao Nagasaki, Ritsuko Shimizu, Jun Yasuda, Hideo Harigae, Masayuki Yamamoto

    BRITISH JOURNAL OF HAEMATOLOGY　176　(2)　318-321　2017年1月

    DOI： 10.1111/bjh.13948 　

    ISSN：0007-1048

    eISSN：1365-2141

  10. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals 査読有り

    Masao Nagasaki, Jun Yasuda, Fumiki Katsuoka, Naoki Nariai, Kaname Kojima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Junji Yokozawa, Inaho Danjoh, Sakae Saito, Yukuto Sato, Takahiro Mimori, Kaoru Tsuda, Rumiko Saito, Xiaoqing Pan, Satoshi Nishikawa, Shin Ito, Yoko Kuroki, Osamu Tanabe, Nobuo Fuse, Shinichi Kuriyama, Hideyasu Kiyomoto, Atsushi Hozawa, Naoko Minegishi, James Douglas Engel, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

    Nature Communications　6　(1)　2015年11月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/ncomms9018 　

    eISSN：2041-1723

  11. Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human population 査読有り

    Ikuko N. Motoike, Mitsuyo Matsumoto, Inaho Danjoh, Fumiki Katsuoka, Kaname Kojima, Naoki Nariai, Yukuto Sato, Yumi Yamaguchi-Kabata, Shin Ito, Hisaaki Kudo, Ichiko Nishijima, Satoshi Nishikawa, Xiaoqing Pan, Rumiko Saito, Sakae Saito, Tomo Saito, Matsuyuki Shirota, Kaoru Tsuda, Junji Yokozawa, Kazuhiko Igarashi, Naoko Minegishi, Osamu Tanabe, Nobuo Fuse, Masao Nagasaki, Kengo Kinoshita, Jun Yasuda, Masayuki Yamamoto

    BMC GENOMICS　15　673　2014年8月

    DOI： 10.1186/1471-2164-15-673 　

    ISSN：1471-2164

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