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mitochondrial function in failed cardiac muscle

Research Project

Project/Area Number 16590671
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

KATOH Hideki  Hamamatsu University School of Medicine, assistant professor, 医学部, 助教 (80314029)

Co-Investigator(Kenkyū-buntansha) SATOH Hiroshi  Hamamatsu University School of Medicine, Senior Associate Professor, 医学部附属病院, 講師 (30293632)
TERADA Hajime  Hamamatsu University School of Medicine, Senior Associate Professor, 医学部附属病院, 講師 (50252177)
HAYASHI Hideharu  Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50135258)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsmitochondria / protein kinase A / membrane potential / heart failure / redox state / reactive oxygen species / 心不全 / 酸化還元状態 / 活性酸素種 / 自家蛍光
Research Abstract

β-adrenergic stimulation acts via cAMP-dependent protein kinase A (PKA) to phosphorylate functional proteins and myofibrils. However, relatively little is known about the relationship between mitochondrial metabolism and PKA in response to (β-adrenergic stimulation. We investigated the effects of PKA on mitochondrial redox state (FAD fluorescence), mitochondrial membrane potential (ΔΨ_m ; measured with TMRE) and ROS production (measured with dichlorofluorescein diacetate (DCF) fluorescence) in saponin-permeabilized rat ventricular myocytes. (1) Application of PKA catalytic subunit (PKA_<cat>) increased FAD intensities, which was inhibited by a PKA inhibitor (PKI). (2) Application of PKA_<cat> depolarized ΔΨ_m. The effect of PKA_<cat> on ΔΨ_m was blocked by PKI. (3) Application of PKA_<cat> increased DCF intensities, which was inhibited by Trolox (a ROS scavenger). (4) PKA_<cat>-induced ΔΨ_m depolarization and FAD elevation were inhibited by Trolox. (5) PKA_<cat>-induced ΔΨ_m, depolarization was inhibited by DIDS (an inhibitor of inner membrane anion channel (IMAC)) but not by CsA (an mPTP inhibitor). These results demonstrated that PKA_<cat> alters mitochondrial redox state and ΔΨ_m via mitochodrial ROS generation. It is also suggested that PKA-induced ΔΨ_m depolarization was not related to mPTP, but to the DIDS sensitive mechanisms, which could be IMAC. The depolarizaticin of ΔΨ_m by PKA might be related to the mitochondrial dysfunction under the condition of extensive β-adrenergic stimulation.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (26 results)

All 2007 2006 2005 2004 Other

All Journal Article (26 results)

  • [Journal Article] Protein kinase A catalytic subunit alters cardiac mitochondrial redox state and membrane potential via the formation of reactive oxygen species.2007

    • Author(s)
      Nagasaka S, Katoh H, Niu CF, Matsui S, Urushida T, Satoh H, Watanabe, Hayashi H
    • Journal Title

      Circulation Journal 72

      Pages: 429-436

    • NAID

      110006224216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Non-genomic effects of aldosterone on intracellular ion regulation and cell volume in rat ventricular myocytes.2007

    • Author(s)
      Matsui S, Satoh H, Kawashima H, Nagasaka S, Niu CF, Urushida T, Katoh H, Watanabe Y, Hayashi H
    • Journal Title

      Can J Physiol Pharmacol 85

      Pages: 264-273

    • 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] Protein kinase A catalytic subunit alters cardiac mitochondrial redox state and membrane potential via the formation of reactive oxygen species.2007

    • Author(s)
      Nagasaka S, Katoh H, Niu CF, Matsui S, Urushida T, Satoh H, Watanabe, Hayashi H
    • Journal Title

      Circulation Journal 71

      Pages: 429-436

    • NAID

      110006224216

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A selective inhibitor of Na^+/Ca^<2+> exchanger, SEA400, preserves cardiac function and high-energy phosphates against ischemia/reperfusion injury.2006

    • Author(s)
      Niu CF, Satoh H, Urushida T, Katoh H, Terada H, Watanabe Y, Hayashi H
    • Journal Title

      J Cardiovasc Pharmacol 47

      Pages: 263-270

    • 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] Arrhythmogenic effects of aarsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles.2006

    • Author(s)
      Yamazaki K, Terada H, Satoh H, Naito K, Takeshita A, Uehara A, Katoh H, Ohnishi K, Hayashi H
    • Journal Title

      Circulation Journal 70

      Pages: 1407-1414

    • 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] Evaluation of right and left ventricular function by quantitative blood-pool SPECT (QBS) : Comparison with conventional methods and quantitative gated SPECT (QGS).2006

    • Author(s)
      Odagiri K, Wakabayashi Y, Tawarahara K, Kurata C, Urushida T, Katoh H, Satoh H, Hayashi H
    • Journal Title

      Ann Nucl Med 20

      Pages: 519-526

    • NAID

      10018396270

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endoplasmic reticulum Ca2+ depletion induces endothelial cell apoptosis independently of caspase-12.2006

    • Author(s)
      Nakano T et al.
    • Journal Title

      Cardiovasc Res 69

      Pages: 908-915

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A selective inhibitor of Na+/Ca2+ exchanger, SEA400, preserves cardiac function and high-energy phosphates against ischemia/reperfusion injury.2006

    • Author(s)
      Niu CF et al.
    • Journal Title

      J Cardiovasc Pharmacol 47

      Pages: 263-270

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Arrhythmogenic effects of aarsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles.2006

    • Author(s)
      Yamazaki K et al.
    • Journal Title

      Circ J 70

      Pages: 1407-1414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endoplasmic reticulum Ca^<2+> depletion induces endothelial cell apoptosis independently of caspase-12.2006

    • Author(s)
      Nakano T, Watanabe H, Ozeki M, Asai M, Katoh H, Satoh H, Hayashi H
    • Journal Title

      Cardiovasc Res 69

      Pages: 908-915

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of right and left ventricular function by quantitative blood-pool SPECT (QBS) : Comparison with conventional methods and quantitative gated SPECT (QGS).2006

    • Author(s)
      Odagiri K, Wakabayashi Y, Tawarahara K, Kurata C, Urushida T, Katoh H, Satoh H, Hayashi H.::, 2006
    • Journal Title

      Ann Nucl Med 20

      Pages: 519-526

    • NAID

      10018396270

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endoplasmic reticulum Ca2+ depletion induces endothelial cell apoptosis independently of caspase-12.2006

    • Author(s)
      Tomoyasu Nakano
    • Journal Title

      Cardiovasc Res. 69

      Pages: 908-915

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A selective inhibitor of Na+/Ca2+ exchanger, SEA0400, preserves cardiac function and high-energy phosphates against ischemia/reperfusion injury.2006

    • Author(s)
      Feng N C
    • Journal Title

      J Cardiovasc Pharmacol 47

      Pages: 263-270

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Post-challenge hyperinsulinemia rather than hyperglycemia is associated with the severity of coronary artery disease in patients without previous diagnosis of diabetes mellitus.2005

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

      Heart 91

      Pages: 731-736

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Modulation of SR Ca2+ release by FK506 induces defective excitation-contraction coupling only when SR Ca2+ recycling is disturbed.2005

    • Author(s)
      Yoshihara S et al.
    • Journal Title

      Can J Physiol Pharmacol 83

      Pages: 357-366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mitochondrial membrane potential modulates regulation of mitochondrial Ca2+ in skinned rat ventricular myocytes.2005

    • Author(s)
      Saotome M et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Usefulness of delayed enhancement magnetic resonance imaging for detecting cardiac rupture caused by small myocardial infarction in a case of cardiac tamponade.2005

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

      Circ J 69

      Pages: 1556-1559

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Post-challenge hyperinsulinaemia rather than hyperglycaemia is associated with the severity of coronary artery disease in patients without a previous diagnosis of diabetes mellitus.2005

    • Author(s)
      Hiroshi Satoh
    • Journal Title

      Heart 91

      Pages: 731-736

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Different actions of cardioprotective agents on mitochondrial Ca^<2+> regulation in a Ca^<2+> paradox-induced Ca^<2+> overload.2005

    • Author(s)
      Masaki Matsunaga
    • Journal Title

      Circulation J. 69

      Pages: 1132-1140

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Usefulness of delayed enhancement magnetic resonance imaging for detecting cardiac rupture caused by small myocardial infarction in a case of cardiac tamponade.2005

    • Author(s)
      Fumitaka Matoh
    • Journal Title

      Circulation J. 69

      Pages: 1556-1559

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mitochondrial membrane potential modulates regulation of mitochondiral Ca^<2+> in skinned rat ventricular myocytes2005

    • Author(s)
      Masao Saotome
    • Journal Title

      Am.J.Physiol. 288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts.2004

    • Author(s)
      Wakahara N et al.
    • Journal Title

      Circ J 68

      Pages: 156-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Usefulness of stress myocardial perfusion imaging for evaluating asymptomatic patients after coronary stent implantation. Circ J : 68 : 462-466, 2004.2004

    • Author(s)
      Sugi T et al.
    • Journal Title

      Circ J 68

      Pages: 462-466

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ML-9, a myosin light chin kinase inhibitor, reduces intracellular Ca2+ concentration in guinea pig trachealis.2004

    • Author(s)
      Ito S et al.
    • Journal Title

      Eur J Pharmacol 486

      Pages: 325-333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts2004

    • Author(s)
      Nobuyuki Wakahara
    • Journal Title

      Circulation J. 68

      Pages: 156-162

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Modulation of SR Ca release by FK506 induces defective excitation-contraction coupling only when SR Ca recycling is disturbed.

    • Author(s)
      Shu Yoshihara
    • Journal Title

      Can.J.Physiol.Pharmacol. (In press)

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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