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Role of epigenetic regulation on female-predominant expression of drug-metabolizing enzyme CYP3A gene

Research Project

Project/Area Number 23590172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

SAKUMA TSUTOMU  富山大学, 大学院医学薬学研究部(薬学), 准教授 (30250468)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Yuki  富山大学, 大学院医学薬学研究部(薬学), 助教 (30432107)
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords性差 / CYP / 発現調節 / マウス / エピジェネティック
Outline of Final Research Achievements

Some of CYP3A genes including human CYP3A4 and mouse Cyp3a41 express female-predominantly. The objective of this study is to clarify the mechanisms, especially epi-genetic manner, for female-predominant expression. Our study demonstrated that female-dominant binding of HNF4a to the promoter (-99/-87) was involved in female specific expression of mouse Cyp3a41 gene. CHART-PCR analysis demonstrated that the chromatin prepared from female mouse hepatocytes was more relaxed than that from male hepatocytes. It is, therefore, likely that this difference is a cause of the female-dominant binding of HNF4a on Cyp3a41 gene. Reporter gene assay demonstrated that COUP-TFII and HNF4a interact in a synergic manner on Cyp3a41 gene in female hepatocytes. Thus, sex difference in chromatin structure and synergistic interaction between HNF4a and COUP-TFII may contribute to the female-specific expression of Cyp3a41 in the livers of mice.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 2013 2012 2011

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (8 results)

  • [Journal Article] p38-Mediated phosphorylation of Eps15 endocytic adaptor protein.2014

    • Author(s)
      Zhou Y., Tanaka T., Sugiyama N., Yokoyama S., Kawasaki Y., Sakuma T., Ishihama Y., Saiki I., and Sakurai H.
    • Journal Title

      FEBS Letters

      Volume: 588 Issue: 1 Pages: 131-137

    • DOI

      10.1016/j.febslet.2013.11.020

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulations of cytochrome P450 expression in diabetic mice by berberine2012

    • Author(s)
      Chatuphonprasert W., Nemoto N., Sakuma T., and Jarukamjorn K.
    • Journal Title

      Chem. Biol. Interact.

      Volume: 196 Issue: 1-2 Pages: 23-29

    • DOI

      10.1016/j.cbi.2012.01.006

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte nuclear factor 4 alpha regulates expression of the mouse female-specific Cyp3a41 gene in the liver2011

    • Author(s)
      Bhadhprasit W., Sakuma T., Kawasaki Y., Nemoto N
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 39 Issue: 3 Pages: 490-497

    • DOI

      10.1124/dmd.110.035980

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modified expression of aryl hydrocarbon receptor-related genes by deoxymiroestrol, a phytoestrogen, in mouse hepatocytes in primary culture2011

    • Author(s)
      Udomsuk L., Jarukamjorn K., Putalun W., Sakuma T., Kawasaki Y., Nemoto N
    • Journal Title

      Journal of Ethnopharmacology

      Volume: 137 Issue: 1 Pages: 902-908

    • DOI

      10.1016/j.jep.2011.06.047

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] マウスCyp1a2遺伝子フェノバルビタール型誘導剤応答領域の解析2015

    • Author(s)
      佐久間勉、河崎優希、古野幸美、後藤雄真、茂木優治、根本信雄、櫻井宏明
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] マウスCyp1a2遺伝子のフェノバルビタール型誘導剤による発現調節機構の解析2014

    • Author(s)
      佐久間勉、河崎優希、古野幸美、後藤雄真、茂木優治、根本信雄、櫻井宏明
    • Organizer
      日本薬学会北陸支部第126回例会
    • Place of Presentation
      石川県金沢市
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高度に保存されているDBD内スレオニンのリン酸化による核内受容体の活性調節2013

    • Author(s)
      佐久間勉,谷翔太,手賀悠真,進藤佐和子,根岸正彦,河崎優希,根本信雄,櫻井宏明
    • Organizer
      フォーラム2013衛生薬学・環境トキシコロジー
    • Place of Presentation
      福岡市
    • Related Report
      2013 Research-status Report
  • [Presentation] 高度に保存されたスレオニンのリン酸化を介したPPARの活性調節機構2013

    • Author(s)
      谷翔太,佐久間勉,手賀悠真,進藤佐和子,根岸正彦,梅嵜雅人,河崎優希,根本信雄,櫻井宏明
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 成長ホルモンおよびグルココルチコイドホルモンによるマウスCyp3a遺伝子発現の比較解析2012

    • Author(s)
      佐久間勉,栗本夕夏,松井友理恵,池松怜美,宅間祐太朗,河崎優希,根本信雄,櫻井宏明
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulatory elements for transcriptional activation of the mouse Cyp1a2 gene by constitutive androstane receptor-ligand2012

    • Author(s)
      Kawasaki Y., Furuno Y., Goto Y., Sakuma T., Sakurai H., and Nemoto N.
    • Organizer
      50TH Anniversary Symposium on Cytochrome P450 in Fukuoka
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Periodic fluctuation of Cyp3a gene expression in the mouse liver2011

    • Author(s)
      Tsutomu Sakuma, Satomi Ikematsu, Yuka Kurimoto, Yuki Kawasaki, Nobuo Nemoto
    • Organizer
      第26回日本薬物動態学会年会
    • Place of Presentation
      広島市
    • Related Report
      2011 Research-status Report
  • [Presentation] マウス全CYP3A分子種のmRNA発現量の比較解析2011

    • Author(s)
      栗本夕夏, 佐久間勉, 宅間祐太郎, 池松怜美, 河崎優希, 櫻井宏明, 根本信雄
    • Organizer
      日本薬学会北陸支部第123回例会
    • Place of Presentation
      金沢市
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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