Epigenetic regulation of sex-specific gene expression and investigation of the effects of environmental chemicals and drugs
| Project/Area Number |
17K08401
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Hiroshima International University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
清水 良 広島国際大学, 薬学部, 講師 (00570491)
太田 茂 広島大学, 医系科学研究科(薬), 名誉教授 (60160503)
渡部 容子 日本薬科大学, 薬学部, 助教 (60628056)
田山 剛崇 広島国際大学, 薬学部, 准教授 (80389121)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 性差 / 薬物代謝酵素 / 成長ホルモン / 内分泌かく乱物質 / 医薬品 / 薬毒物代謝酵素 / 転写制御 / ホルモン / 系統差 / シトクロムP450 / アルデヒドオキシダーゼ / エピジェネティクス |
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| Outline of Final Research Achievements |
The strain and sex differences in the expression of aldehyde oxidase (AOX), a drug metabolizing enzyme, were investigated in mice. The strain and sex differences were mainly due to variation in the expression of AOX3, which is AOX isozyme specifically expressed in mice. AOX molecular species expressed in mouse liver. Significantly different sequences were found in the upstream region of the AOX3 gene in different strains. We found that growth hormone (GH) exposure to mouse hepatocarcinoma cells Hepa1-6 was able to replicate the sex difference in vivo mouse.
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| Academic Significance and Societal Importance of the Research Achievements |
薬毒物の影響や疾病などに性差があることが知られているが、性差発現メカニズムの多くが未解明である。本研究では、マウスの様々な系統やマウス肝がん細胞を用いて、薬毒物代謝酵素の1つであるアルデヒド酸化酵素(AOX)の発現における系統差および性差について調査を行った。マウスではAOX分子種のうちAOX1と3が発現しているが、性差および系統差は主にAOX3の変動であることを明らかとした。AOX3は成長ホルモンや性ホルモンの他、内分泌かく乱物質による影響も受けることを見出した。AOX3の遺伝子上流配列の違いも見出しており、これらが性差、系統差に関連することを解明している
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear receptors2019
Author(s)
Hiroyuki Kojima, Shinji Takeuchi, Seigo Sanoh, Katsuhiro Okuda, Shigeyuki Kitamura, Naoto Uramaru, Kazumi Sugihara, Kouichi Yoshinari
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Journal Title
Toxicology, 413(2),48-55,
Volume: 413
Pages: 48-55
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Developmental changes in drug-metabolizing enzyme expression during metamorphosis of <i>Xenopus tropicalis </i>2017
Author(s)
Mori J., Sanoh S., Kashiwagi K., Hanada H., Shigeta M., Suzuki K., Yamamoto T., Kotake Y., Sugihara K., Kitamura S., Kashiwagi A., Ohta S.
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Journal Title
The Journal of Toxicological Sciences
Volume: 42
Issue: 5
Pages: 605-613
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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[Presentation] Assessment of inhibitory effects of drugs on mouse and human aldehyde oxidases through in silico, in vitro, and in vivo approaches.2018
Author(s)
Naoki Takaoka, Seigo Sanoh, Katsuhiro Okuda, Go Sugahara, Ami Yanagi, Yuji Ishida, Chise Tateno, Yoshitaka Tayama, Kazumi Sugihara, Shigeyuki Kitamura, Mami Kurosaki, Mineko Terao, Enrico Garattini, Shigeru Ohta, Yaichiro Kotake
Organizer
2018 International Meeting on 22nd MDO and 33rd JSSX
Related Report
Int'l Joint Research
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