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Changes in cytochrome P450 and stress responsive proteins under oxidative stress

Research Project

Project/Area Number 13672347
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionShowa university

Principal Investigator

YOSHIDA Takemi  Showa Univ. Sch. Pharmaceut. Sci., Professor, 薬学部, 教授 (20138415)

Co-Investigator(Kenkyū-buntansha) ASHINO Takashi  Showa Univ. Sch. Pharmaceut. Sci., Assistant, 薬学部, 助手 (00338534)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordscytochromeP450 / heme oxygenese-1 / cytokine / oxidative stress / MAPK / BCG / LPS / STAT / TNFα / IL-6
Research Abstract

The purpose of this study was to explore the roles of cytokines in the regulation of cytochrome P450(CYP) stress responsive enzyme heme oxygenase-1(HO-1).We examined the effect of each cytokine on their target cells,especially the expression of HO-1 and CYP in the liver of IL-1α/β(IL-1),TNFα and IL-6 knockout(KO) mice.We found that TNFα played an important role in HO-1 gene expresssion by LPS.Based on these findings, we also examined major signal transduction from LPS in cytokine knockout mice. LSP has been shown to lead HO-1 gene expression via activation of AP-1. Therefore,we determined the effect of LPS on signal transduction from MAPK cascade leading to HO-1 gene expression in TNFα KO mice,which produced little response to the agent. We found that TNFα plays actively in the LPS-mediated induction of HO-1 gene expression, and its signal is conducted via p38 and/or JNK.In addition, cocaine-mediated HO-1 was modulated not only TNFα but also IL-6.Moreover, we clarified the important role of cytokines was in BCG-mediated down-regulation of CYP3A
and penobarbital-mediated induction of CYP2B by using cytokine KO mice. Suggesting IL-6 is an important factor for CYP regulation. This study thus indicate that cytokine KO mice are very useful in vivo model to explain their roles in the regulation of CYP and HO-1 Comprehensive study on enzyme indication and stress response and their signal transduction in cytokine KO mice could lead to exploit the significant role of each cytokine played vivo.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] 小黒 多希子: "Involvement of Tumor Necrosis Factor α, rather than Interleukin-1 α/β or Nitric Oxides in the Heme oxygenase-1 Gene Expression by Lipopolysaccharide in the Mouse Liver"FEBS Letters.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takiko Oguro: "Involvement of tumor necrosis factorα, rather then interleukin-1α/β or nitric oxides in the the heme oxigenase-1 gene expression by lipopolysaccharide in the mouse liver"FEBS Letters. 516. 63-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 小黒 多希子: "Involvement of Tumor Necrosis Factor α, rather than Interleukin-1 α/βor Nitric Oxides in the Heme oxygenase-1 Gene Expression by Lipopolysaccharide in the Mouse Liver"FEBS Letters. 516. 63-66 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小黒 多希子: "Involvement of Tumor Necrosis Factor α, rather than Interleukin-1α/β or Nitric Oxides in the Heme oxygenase-1 Gene Expression by Lipopolysaccharide in the Mouse Liver"FEBS Letters.

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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