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Role of oxidative stress and the JNK pathway in diabetes

Research Project

Project/Area Number 17390263
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionOsaka University

Principal Investigator

MATSUHISA Munehide (2006)  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60362737)

山崎 義光 (2005)  大阪大学, 医学系研究科, 助教授 (40201834)

Co-Investigator(Kenkyū-buntansha) MATSUOKA Takaaki  Osaka University, Graduate School of Medicine, Specially Appointed Assistant, 医学系研究科, 特任助手 (10379258)
松久 宗英  大阪大学, 医学系研究科, 助手 (60362737)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥8,700,000 (Direct Cost: ¥8,700,000)
Keywordsdiabetes / pancreatic beta-cells / oxidative stress / JNK pathway / PDX-1 / insulin / Foxol / Rho-kinase / RhoA / 膵beta細胞 / 核外移行 / アデノウイルス
Research Abstract

It has been shown that oxidative stress and activation of the c-Jun N-terminal kinase (JNK) pathway induce the nucleo-cytoplasmic translocation of the pancreatic transcription factor PDX-1, which leads to pancreatic β-cell dysfunction. In this study, we show that the forkhead transcription factor Foxol/FKHR plays a role as a mediator between the JNK pathway and PDX-1. Under oxidative stress conditions, Foxol changed its intracellular localization from the cytoplasm to the nucleus in the pancreatic β-cell line HIT-T15. The overexpression of JNK also induced the nuclear localization of Foxol, but in contrast, suppression of JNK reduced the oxidative stress-induced nuclear localization of Foxol, suggesting the involvement of the JNK pathway in Foxol translocation. In addition, oxidative stress or activation of the JNK pathway decreased the activity of Akt in HIT cells, leading to the decreased phosphorylation of Foxol following the nuclear localization of Foxol. Furthermore, adenovirus-mediated Foxol overexpression reduced the nuclear expression of PDX-1, whereas repression of Foxol by Foxol-specific siRNA retained the nuclear expression of PDX-1 under oxidative stress conditions. Taken together, Foxol is involved in the nucleo-cytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (5 results)

All 2006

All Journal Article (5 results)

  • [Journal Article] The forkhead transcription factor Foxol bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation.2006

    • Author(s)
      Kawamori D, Kaneto H, Nakatani Y, Matsuoka T, Matsuhisa M, Hori M, Yamasaki Y
    • Journal Title

      J. BioL Chem. 281

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Marked increase of insulin gene transcription by suppression of the Rho/Rho-kinase pathway.2006

    • Author(s)
      Nakamura Y, Kaneto H, Miyatsuka T, Matsuoka T, Matsuhisa M, Node K, Hori M, Yamasaki Y.
    • Journal Title

      Biochem. Biophys. Res. Commun. 350・1

      Pages: 68-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The forkhead transcription factor Foxol bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation2006

    • Author(s)
      Kawamori D, Kaneto H, Nakatani Y, Matsuoka T, Matsuhisa M, Hori M, Yamasaki Y
    • Journal Title

      J.Biol.Chem. 281

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Marked increase of insulin gene transcription by suppression of the Rho/Rho-kinase pathway2006

    • Author(s)
      Nakamura Y, Kaneto H, Miyatsuka T, Matsuoka T, Matsuhisa M, Node K, Hori M, Yamasaki Y.
    • Journal Title

      Biochem.Biophys.Res.Commu. 350(1)

      Pages: 68-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation.2006

    • Author(s)
      Kawamori D, Kaneto H, Nakatani Y, Matsuoka T, Matsuhisa M, Hori M, Yamasaki Y
    • Journal Title

      J.Biol.Chem. 281

      Pages: 1091-1098

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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