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Research in the mechanism of ischemic cell death of cardiomyocyte and the role of mitochondria

Research Project

Project/Area Number 13670716
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYamaguchi University

Principal Investigator

IKEDA Yasuhiro (2002)  Yamaguchi University School of Medicine, Assistant Prof., 医学部, 寄附講座教員 (00260349)

三浦 俊郎 (2001)  山口大学, 医学部, 講師 (00243634)

Co-Investigator(Kenkyū-buntansha) MIURA Toshiro  Yamaguchi University School of Medicine, Associate Prof., 医学部, 講師 (00243634)
池田 安宏  山口大学, 医学部・附属病院, 医員(臨床)
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: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsIschemia / reperfusion injury / mitochondria / intracellular calcium / superoxide / potassium channel / preconditioning / protein kinase C / Ischemic preconditioning / ミトコンドリアK-ATPchannel / ベータ遮断薬 / Ca paradox / 低体温 / アポトーシス / ischemic preconditioning / 心筋梗塞 / protein kinase C / adenylate kinase / 膜電位
Research Abstract

In the rat ischemia-reperfusion model, the effect of ischemic preconditioning, mitochondrial K-ATP channel openers, nicorandil and diazoxide, on the reduction of infarct size was tested. All these interventions reduced the infarct size significantly, indicating the importance of the opening of mitochondrial K-ATP cahnnels for the reduction of ischemic injury. The left ventricular remodeling was assessed by the LV pressure-volume relation at 3 weeks after infarction. The LV remodeling was attenuated by the opening of mitochondrial K-ATP channels and the extent of remodeling and infarct size was correlated. The mechanism of opening the mitochondrial K-ATP channels is distinct between nicorandil and diazoxide, since the effect of nicorandil was partially inhibited by PKC inhibitor, although the effect of diazoxide was not influenced. The PKC isoform translocation from cytosolic to mitochondrial fraction was assessed by Western blotting. This revealed that the PKC ε and δ was translocated to mitochondrial fraction by nicorandil, which is inhibited by PKC inhibitor. Furthermore, NO quencher reduced the translocation of these isoforms to the mitochondrial fraction indicates that the NO donor effect of nicorandil activates the PKC ε and δ, which subsequently activates the mitochondrial K-ATP cahnnels synergistically with the direct opening effect of nicorandil. The adaptor protein in mitochondria which bind to PKC ε and δ were explored by immunoprecipitation and new adaptor proteins are detected, which may play an important role for the activation of mitochondrial K-ATP channels.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Yuaka Dairaku: "Effect of Ischemic preconditioning and mitochondrial K-ATP channel openers on chronic left ventricular remodeling in the ischemic-reperfused rat heart"Circulation J. 66. 411-415 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoichi Mizukami: "Phosphorylation of proteins and apoptosis induced by c-jun N-terminal kinase 1 activation in rat cardiomyocytes by H_2O_2 stimulation"Biochimica et Biophysica Acta. 1540. 213-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 三浦俊郎: "虚血再灌流後の心筋梗塞サイズと左室リモデリングに及ぼすcaspase経路およびミトコンドリアK-ATPチャネルの影響について"Ther Res. 22. 2118-2123 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiro Miura: "Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia"Circulation. 104. 1053-1058 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masayasu Kimura: "Orphan G protein-coupled receptor, GPR41, induces apoptosis via a p53/Bax pathway during ischemic hypoxia and reoxygenation"J Biol Chem. 276. 26453-26460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mitsuo Iwatate: "Effects of in vivo gene transfer of fibroblast growth factor-2 on cardiac function and collateral vessel formation in microembolized rabbit heart"Jpn Circ J. 65. 226-231 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 三浦俊郎: "心臓における生命現象の分子生物学"メディカルビュー社. 242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuaka Dairaku, Toshiro Miura, Yasuhiro Ikeda, et al.: "Effect of Ischemic preconditioning and mitochondrial K-ATP channel openers on chronic left ventricular remodeling in the ischemic-reperfused rat heart"Circulation J.. 66. 411-415 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoichi Mizukami, Takayuki Okamura, Toshiro Miura, et al.: "Phosphorylation of proteins and apoptosis induced by c-jun N-terminal kinase 1 activation in rat cardiomyocytes by H_20_2 stimulation"Biochimica et Biophysica Acta. 1540. 213-220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiro Miura: "Effect of caspase pathway and mitochondrial K-ATP channel on the infarct size and left ventricular remodeling in rat."Ther Res. 22. 2118-2123 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiro Miura, Yasuhiro Ikeda, et al.: "Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia"Circulation. 104. 1053-1058 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masayasu Kimura, Yoichi Mizukami, Toshiro Miura, et al.: "Orphan G protein-coupled receptor, GPR41, induces apoptosis via a p53/Bax pathway during ischemic hypoxia and reoxygenation"J. Biol. Chem.. 276. 26453-26460 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mitsuo Iwatate, Toshiro Miura, Yasuhiro Ikeda, et al.: "Effects of in vivo gene transfer of fibroblast growth factor-2 on cardiac function and collateral vessel formation in microembolized rabbit heart"Jpn. Circ. J.. 65. 226-231 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiro Miura: "Molecular biology of the heart"Medical View. 1-242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiro Miura: "Isehemic Preconditioning Attenuates Cardiac Sympathetic Nerve Injury via ATP-Sensitive Potassium Channels During Myocardial Ischemia"Circulation. 104・9. 1053-1058 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuka Dairaku: "Effect of Ischemic Preconditioning and Mitochondrial K_<ATP> Channel Openers On Chrnic Left Ventricular Remodering in the Ischemic-Reperfused Rat Heart"Circulation Journal. 66・4. 411-415 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshiro Miura: "Ischemic preconditioning attenuates injury of cardiac sympathetic nerve terminals via ATP-sensitive potassium chanels during myocardial ischemia."Circulation. 104. 1053-1058 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuka Dairaku: "Effect of ischemic preconditioning and mitochondorial K-ATP channel openers on chronic left ventricular remodeling in ischemic-reperfused rat heart"Circulation J. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoichi Mizukami: "Phosphorylation of proteins and apoptosis induced by c-Jun N-terminal Kinase 1 activation in rat cardiomyocytes by H202 stimulation."Biochimi Biophysi Acta. 1540. 213-220 (2001)

    • Related Report
      2001 Annual Research Report

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

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