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Bioimaging analysis of hypoxic cell death and its cellular defense mechanisms.

Research Project

Project/Area Number 15390061
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionYamagata University

Principal Investigator

TAKAHASHI Eiji  Yamagata University, School of Medicine, Associate Professor, 医学部, 助教授 (30206792)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Katsuyuki  Hokkaido University, Graduate School of Engineering, Professor, 大学院・工学研究科, 教授 (10088867)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsoxygen / heart / mitochondria / creatine kinase / hypoxia / ischemia / bioimaging / ATP / 生理学 / 心筋細胞 / クレアチンリン酸 / クレアチンリン酸シャトル / GFP / 蛍光画像 / 分光画像
Research Abstract

In single cardiomyocytes isolated from the adult rat, we investigated changes in intracellular oxygen concentration, mitochondrial oxidative metabolism, intracellular ATP concentration, and mitochondrial membrane potential using newly devised fluorescence imaging system. At physiological oxygen concentration (3%-5%),elevating oxygen flux to mitochondria by an uncoupler of oxidative phosphorylation promoted necrotic cell death. Because changes in the mitochondrial membrane potential in these cells were minimum, increases in the oxygen flux appeared to critically affect cell survival in hypoxia. Observed cell death was significantly accelerated after inhibition of creatine kinase (CK). In CK-inhibited cardiomyocytes with elevated oxygen flux, membrane potential was almost abolished in the cell core that is consistent with our previous findings regarding radial gradients of oxygen concentration within a single cardiomyocyte (anoxic cell core). Disruption of mitochondrial membrane potentia … More l in the anoxic core would turn the F_1F_0-ATP synthase (complex V) to an ATPase. If these happen, not only oxidative ATP production would be unable to proceed, but also massive consumption of ATP should break out in mitochondria in the anoxic core. This deficiency of ATP, albeit restricted in the cell core, quickly disturbs ATPase-dependent intracellular regulations of Ca^<2+>, and Ca^<2+> overload leading to cell death would finally commence. However, in the normal cardiomyocyte, the PCr-CK system may supply high energy phosphate from the cell surface (where oxygen is abundant and oxidative ATP production is not hampered) to the oxygen deficit cell core by diffusion. Thus, PCr originally produced in mitochondria near the cell surface would supplement ATP to the mitochondria in the anoxic cell core, so that mitochondrial membrane potential is maintained without electron transport in the respiratory chain. Functional disintegration of the mitochondria and following Ca^<2+> overload could be significantly retarded by this mechanism. Hence, the PCr-CK system may be an intrinsic mechanism that protects respiring cardiomyocytes against hypoxic death. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2006 2005 Other

All Journal Article (12 results) Book (3 results) Publications (1 results)

  • [Journal Article] In vivo oxygen imaging using green fluorescent protein.2006

    • Author(s)
      takahashi E
    • Journal Title

      Am J Physiol Cell Physiol 291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HIF-1α as a target for drug design in ischemic injury : effect of cobalt treatment on mitochondrial DNA damage in cells exposed to H_2 O_2.2006

    • Author(s)
      Nomura Y
    • Journal Title

      Lett Drug Des Discov 3

      Pages: 172-174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo oxygen imaging using green fluorescent protein.2006

    • Author(s)
      Takahashi E et al.
    • Journal Title

      Am J Physiol Cell Physiol 291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HIF-1 a as a target for drug design in ischemic injury : effect of cobalt treatment on mitochondrial DNA damage in cells exposed to H2O2.2006

    • Author(s)
      Nomura Y et al.
    • Journal Title

      Lett Drug Des Discov 3

      Pages: 172-174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GFP as an indicator of intracellular oxygenation.2005

    • Author(s)
      Takahashi E
    • Journal Title

      Adv Exp Med Biol 566

      Pages: 39-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aged mouse oocytes fail to readjust intracellular ATP at fertilization.2005

    • Author(s)
      Igarashi H
    • Journal Title

      Biol Reprod 77

      Pages: 1256-1261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genetic oxygen sensor. GFP as an indicator of intracellular oxygenation.2005

    • Author(s)
      Takahashi E et al.
    • Journal Title

      Adv Exp Med Biol 566

      Pages: 39-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aged mouse oocytes fail to readjust intracellular ATP at fertilization.2005

    • Author(s)
      Igarashi H et al.
    • Journal Title

      Biol Reprod 77

      Pages: 1256-1261

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aged mouse oocytes fail to readjust intracellular adenosine triphosphate at fertilization.2005

    • Author(s)
      Igarashi H
    • Journal Title

      Biology of Reproduction 77

      Pages: 1256-1261

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genetic oxygen sensor. GFP as an indicator of intracellular oxygenation.2005

    • Author(s)
      Takahashi E
    • Journal Title

      Advances in Experimental Medicine and Biology 556

      Pages: 39-44

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aged Mouse Oocytes Fail to Readjust Intracellular Adenosine Triphosphates at Fertilization2005

    • Author(s)
      Igarashi H et al.
    • Journal Title

      Biol Reprod (on lineにて先行出版)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo oxygen imaging by green fluorescent protein.

    • Author(s)
      Takahashi E
    • Journal Title

      American Journal of Physiology : Cell Physiology (accepted)

    • Related Report
      2005 Annual Research Report
  • [Book] 呼吸の事典2006

    • Author(s)
      高橋 英嗣
    • Total Pages
      744
    • Publisher
      5. 酸素と呼吸
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 呼吸の事典2006

    • Author(s)
      高橋英嗣
    • Total Pages
      728
    • Publisher
      朝倉出版
    • Related Report
      2005 Annual Research Report
  • [Book] 呼吸の辞典、22.酸素と呼吸

    • Author(s)
      高橋英嗣
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2004 Annual Research Report
  • [Publications] Takahashi E, et al.: "Genetic oxygen sensor. GFP as an indicator of intracellular oxygenation"Adv Exp Med Biol. (in press).

    • Related Report
      2003 Annual Research Report

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

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