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Molecular biological studies on the mechanisms of the intrinsic cardioprotection system

Research Project

Project/Area Number 15591640
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNagasaki University

Principal Investigator

TOMIYASU Shiro  Nagasaki University, University Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (90244061)

Co-Investigator(Kenkyū-buntansha) CHO Sungsam  Nagasaki University, University Hospital of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (90325655)
MAEKAWA Takuji  Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (10336167)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsCardioprotection / Antioxidant / Glutaredoxin / Akt / Redox / Apoptosis / GAPDH / 酸化ストレス
Research Abstract

Although the role of oxidative stress in cardiovascular disease is well established, the protective mechanisms of antioxidants remain poorly defined. The members of thiol-disulfide oxidoreductases act as cytoprotective antioxidants. One of the most important thiol-disulfide oxidoreductases is glutaredoxin (GRX).
We demonstrated that overexpression of GRX protected cells from hydrogen peroxide (H_2O_2)-induced apoptosis by regulating the redox state of Akt. Akt was transiently phosphorylated, dephosphorylated, and then degraded in cardiac H9c2 cells undergoing H_2O_2-induced apoptosis. Under stress, Akt underwent disulfide・bond formation between Cys297 and Cys311 and dephosphorylation in accordance with an increased association with protein phosphatase 2A (PP2A). Overexpression of GRX protected Akt from H_2O_2-induced oxidation and suppressed recruitment of PP2A to Akt, resulting in a sustained phosphorylation of Akt and inhibition of apoptosis. This effect was reversed by cadmium, an inhibitor of GRX. Thus, GRX plays an important role in cardioprotection by protecting cells from apoptosis through the regulation of the redox state of Akt.
Now, we are investigating the redox regulation of glyceraldehyde-3-phosphate dehydrogenase by GRX.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (8 results)

All 2005

All Journal Article (8 results)

  • [Journal Article] Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca+ exchanger, on stunned myocardium in anesthetized dogs2005

    • Author(s)
      Osamu Yoshitomi
    • Journal Title

      Journal of Anesthesia 19

      Pages: 124-130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of dogs2005

    • Author(s)
      Takuji Maekawa
    • Journal Title

      Journal of Anesthesia 19

      Pages: 136-141

    • NAID

      10015697102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of dexmedetomidine of left ventricular function during hypoxia and reoxygenation on isolated rat hearts2005

    • Author(s)
      Huan Guo
    • Journal Title

      Anesthesia and Analgesia 100

      Pages: 629-635

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Isoflurane administered during early reperfusion protects against myocardial infarction by activating mitochondrial ATP-sensitive K channel in rats2005

    • Author(s)
      Shinya Tosaka
    • Journal Title

      Anesthesiology 103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preischemic administration of milrinone provides protection against ischemia-reperfusion-induced myocardial stunning and arrhythmias in anesthetized swine2005

    • Author(s)
      Tadasuke Use
    • Journal Title

      Anesthesiology 103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cardioprotective effects of sivelestat sodium hydrate on myocardial stunning in swine2005

    • Author(s)
      Daiji Akiyama
    • Journal Title

      Anesthesiology 103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cardioprotective effects of KB-R7943, a novel inhibitor of Na^+/Ca^+ exchanger, on stunned myocardium in anesthetized dogs2005

    • Author(s)
      Osamu Yoshitomi
    • Journal Title

      Journal of Anesthesia 19

      Pages: 124-130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of dexmedetomidine on left ventricular function during hypoxia and reoxygenation in isolated rat hearts2005

    • Author(s)
      Huan Guo
    • Journal Title

      Anesthesia and Analgesia 100

      Pages: 629-635

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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