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Role of nuclear receptors PXR and CAR under the energy surplus condition such as obesity

Research Project

Project/Area Number 19790114
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

YOSHINARI Kouichi  Tohoku University, 大学院・薬学研究科, 准教授 (60343399)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords薬物代謝学 / 核内受容体 / 転写調節 / エネルギー代謝 / コレステロール合成酵素 / DHCR24 / SREBP / HNF4 / レポーターアッセイ / コレステロール / 薬物代謝酵素 / 肝臓 / マウス
Research Abstract

本研究では、薬物応答性の核内受容体CARおよびPXRはコレステロール合成に関わる酵素の遺伝子発現調節を正に調節すること、また、マウスの主要な薬物代謝酵素Cyp3a11の発現はコレステロール欠乏により活性化される転写因子SREBPにより抑制的に制御されることが明らかとなった。これらの結果は、脂質代謝と薬物代謝の間に転写調節因子を介したクロストークが存在することを示唆している。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (24 results)

All 2009 2008 2007

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (6 results)

  • [Journal Article] Unveiling a new essential cis-element for the transactivation of the CYP3A4 gene by xenobiotics2009

    • Author(s)
      T. Toriyabe, K. Nagata, T. Takada, Y. Aratsu, T. Matsubara, K Yoshinari, and Y. Yamazoe
    • Journal Title

      Mol Pharmacol 75

      Pages: 677-684

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of enzymatic N-hydroxylation and reduction in flutamide metabolite-induced liver toxicity2009

    • Author(s)
      M. Ohbuchi, M. Miyata, D. Nagai, M. Shimada, K. Yoshinari, and Y. Yamazoe
    • Journal Title

      Drug Metab Dispos 37

      Pages: 97-105

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unveiling a new essential cis-element for the transactivation of the CYP3A4 gene by xenobiotics2009

    • Author(s)
      T. Toriyabe, et.al.
    • Journal Title

      Mol Pharmacol 75

      Pages: 677-684

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of enzymatic N-hydroxylation and reduction in flutamide metabolite-induced liver toxicity2009

    • Author(s)
      M. Ohbuchi, et.al.
    • Journal Title

      Drug Metab Dispos 37

      Pages: 97-105

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bile acid-induced elevated oxidative stress in the absence of farnesoid X receptor2008

    • Author(s)
      M. Nomoto, M. Miyata, S. Yin, Y. Kurata, M. Shimada, K. Yoshinari, F. J. Gonzalez, K. Suzuki, S. Shibasaki, T. Kurosawa, and Y. Yamazoe
    • Journal Title

      Biol Pharm Bull 32

      Pages: 172-178

    • NAID

      110007042166

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of ST1B subfamily of cytosolic sulfotransferase in kynurenine metabolism to form natriuretic xanthurenic acid sulfate2008

    • Author(s)
      L. Senggunprai, K. Yoshinari, M. Shimada, and Y. Yamazoe
    • Journal Title

      J Pharmacol Exp Ther 327

      Pages: 789-798

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo2008

    • Author(s)
      T. Matsubara, K. Yoshinari, K. Aoyama, M. Sugawara, Y. Sekiya, K. Nagata, and Y. Yamazoe
    • Journal Title

      Drug Metab Dispos 36

      Pages: 2058-2063

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements2008

    • Author(s)
      K. Yoshinari, R. Ueda, K. Kusano, T. Yoshimura, K. Nagata, and Y. Yamazoe
    • Journal Title

      Biochem Pharmacol 76

      Pages: 139-145

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bile acid-induced elevated oxidative stress in the absence of farnesoid X receptor.2008

    • Author(s)
      M. Nomoto, et.al.
    • Journal Title

      Biol Pharm Bull 32

      Pages: 172-178

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of ST1B subfamily of cytosolic sulfotransferase in kynurenine metabolism to form natriuretic xanthurenic acid sulfate2008

    • Author(s)
      L. Senggunprai, et.al.
    • Journal Title

      J Pharmacol Exp Ther 327

      Pages: 789-798

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Umeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements2008

    • Author(s)
      K. Yoshinari, et.al.
    • Journal Title

      Biochem Pharmacol 76

      Pages: 139-145

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo2008

    • Author(s)
      T. Matsubara, et.al
    • Journal Title

      Drug Metab Dispos 36

      Pages: 2058-2063

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ME3738 protects against lithocholic acid-induced hepatotoxicity, which is associated with enhancement of biliary bile acid and cholesterol output2007

    • Author(s)
      M. Nomoto, M. Miyata, M. Shimada, K. Yoshinari, F.J. Gonzalez, S. Shibasaki, T. Kurosawa, Y. Shindo, and Y. Yamazoe
    • Journal Title

      Eur J Pharmacol 574

      Pages: 192-200

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of human hepatocyte nuclear factor 4a in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA2007

    • Author(s)
      Y. Kamiyama, T. Matsubara, K. Yoshinari, K. Nagata, H. Kamimura, and Y. Yamazoe
    • Journal Title

      Drug Metab Pharmacokinet 22

      Pages: 287-298

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of human pregnane X receptor-involvement in pesticide-mediated activation of CYP3A4 gene2007

    • Author(s)
      T. Matsubara, W. Noracharttiyapot, T. Toriyabe, K. Yoshinari, K. Nagata, and Y. Yamazoe
    • Journal Title

      Drug Metab Dispos 35

      Pages: 728-733

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] ME3738 protects against lithocholic acid-induced hepatotoxicity, which is associated with enhancement of biliary bile acid and cholesterol output.2007

    • Author(s)
      M Nomoto, M Miyata, M Shimada, K Yoshinari, FJ Gonzalez, S Shibasaki, T Kurosawa, Y Shindo, Y Yamazoe
    • Journal Title

      European Journal of Pharmacology 574

      Pages: 192-200

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of human hepatocyte nuclear factr 4a in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA.2007

    • Author(s)
      Y Kamiyama, T Matsubara, K Yoshinari, K Nagata, H Kamimura, Y Yamazoe
    • Journal Title

      Drug Metabolism and Pharmacokinetics 22

      Pages: 287-298

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of human pregnane X receptor-involvement in pesticide-mediated activation of CYP3A4 gene.2007

    • Author(s)
      T Matsubara, W Noracharttiyapot, T Toriyabe, K Yoshinari, K Nagata, Y Yamazoe
    • Journal Title

      Drug Metabolism and Disposition 35

      Pages: 728-733

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 薬物応答性核内受容体と医薬品副作用2009

    • Author(s)
      吉成浩一
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] リトコール酸によるCYP3A誘導におけるビタミンD受容体の役割2008

    • Author(s)
      松原勤、吉成浩一、青山和誠、菅原実香、関谷裕次、永田清、山添康
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-31
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 外来異物によるCYP3A4遺伝子の転写活性化に必須な新規シスエレメント2008

    • Author(s)
      鳥谷部貴祥、高田智成、荒津佑輔、松原勤、吉成浩一、永田清、山添康
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-31
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] CARによるヒトCYP1A1およびCYP1A2遺伝子の転写活性化2008

    • Author(s)
      依田典朗、吉成浩一、山添康
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 食餌中の糖・脂質レベルが肝チトクロムP450発現レベルに及ぼす影響2008

    • Author(s)
      菅原実香、吉成浩一、山添康
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction2008

    • Author(s)
      Tsutomu Matsubara, Kouichi Yoshinari, Kazunobu Aoyama, Mika Sugawara, Yuji Sekiya, Kiyoshi Nagata, Yasushi Yamazoe
    • Organizer
      ISSX 15th North American Regional Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2008 Annual Research Report 2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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