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Role of Calcium Signaling Pathway for Cardiac Cell Injury

Research Project

Project/Area Number 05304033
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

TADA Michihiko  Osaka Univ., Medical School., Professor, 医学部, 教授 (90093434)

Co-Investigator(Kenkyū-buntansha) ENDO Masao  Yamagata Univ., Medical School., Professor, 医学部, 教授 (40004668)
TSUKITA Shoichiro  Kyoto Univ., Medical School., Professor, 医学部, 教授 (50155347)
TOYAMA Junji  Nagoya Univ., Inst.of Enviomment Medicine., Prof., 環境医学研究所, 教授 (20023658)
HORI Masatsugu  Osaka Univ., Medical School., Associate Prof., 医学部, 講師 (20124779)
KUZUYA Tsunehiko  Osaka Univ., Medical School., Associate Prof., 医学部, 助教授 (80150340)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsAdhesion molecule / Calcium signaling / Myocardial injury / Reperfusion / Heart failure / Low molecuar weight G-protein / Intercalated disc / Gap junction / 病態生理学 / ホスホランバン / カルシウムポンプ / アラキドン酸 / カルシウム遊離チャネル
Research Abstract

In cardiac muscle, calcium plays a key role in excitation-contraction coupling. In this study, we investigated contribution of the proteins mediating excitation-contraction coupling for myocardial injury.
We identified the interaction sites in phospholamban and the Ca ATPase molecule by using molecular biological methods. We investigated gene regulation of phospholamban and the Ca ATPase, indicating thyroid hormone is a key foactor for the regulation of those gene expression. Regulator binding domain was identified in the Ca release channel of the cardiac sarcoplasmic reticulum. Electrophysiological study on gap junction showed that the activity of gap junction is regulated by calmodulin. We purified and determined the primary structure of adherens junction proteins. We showed that a low molecular weight G-protein, rho regulates cell shape and mobility via actomyosin system.
Calcium overload is a dominating factor for reperfusion injury of myocardium. This might mediated by Ca-dependent proteinase.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] ToyoFuku,et al: "Amino Acids Lys-Asp-Asp-Lys-Pro-Val^<402> in the Ca^<2+>-ATPase of Cardiac Sarcoplasmic Reticulum Are Cretical for Functional Association with Phospholamban." J.Biol.Chem. 269. 22929-22932 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toyama,et al: "Ca^<2+>-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig heart." J.Mol.Cell.Cardiol.26. 1007-1015 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takai,et al: "Rac p^<21> is involved in insulin-induced membrane ruffing and rho p^<21> is involved in hepatocyte growth factor-and 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced membrane ruffling in KB cells." Mol.Cell.Biol.14. 2447-2456 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukita,et al: "Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions." J.Cell.Biol.in press (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sasayama,et al: "Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium:evidence from aequorin-loaded ferret ventricular muscles." J.Clin.Invest.93. 1275-1284 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Serizawa,et al: "Nitric oxide-mediated effects of interleukin 6 on [Ca^<2+>]i and cell contraction in cultured chick embryo ventricular myocytes." Circ.Res.75. 285-295 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toyofuku T.et al: "Amino Acids Lys-Asp-Asp-Lys-Pro-Val^<402> in the Ca^<2+>-ATPase of Cardiac Sarcoplasmic Reticulum Are Cretical for Functional Association with Phospholamban." Biol Chem. 269. 22929-22932 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toyama J.et al: "Ca^<2+>-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig heart." J Mol Cell Cardiol. 26. 1007-1015 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takai Y.et al: "Rac p^<21> is involved in insulin-induced membrane ruffing and rho p^<21> is involved in hepatocyte growth factor- and 12-0-tetradecanoylphorbol-13-acetate (TPA) -induced membrane ruffling in KB cells." Mol Cell Biol. 14. 2447-2456 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sasayama S.et al: "Soudium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium : evidence from aequorin-loaded ferret ventricular muscles." J Clin Invest. 93. 1275-1284 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Serizawa T.et al: "Nitric oxide-mediated effects of interleukin 6 on [Ca^<2+>] i and cell contraction in cultured chick embryo ventricular myocytes." Circ Res. 75. 285-295 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukita S.et al: "Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions." J Cell Biol. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toyofuku,et al: "Amino Acids Glu^2 to lle^<18> in the Cytoplasmic Domain of Phospholamban Are Essential for Functional Association with the Ca^<2+>-ATPase of Sarcoplasmic Reticulum." J.Biol.Chem.269. 3088-3094 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toyama,et al: "Ca^<2+>-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from quinea pig heart." J.Mol.Cell.Cardiol.26. 1007-1015 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sasayama,et al: "Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium:evidence from aequorin-loaded ferret ventricular muscles." J.Clin.Invest.93. 1275-1284 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hidaka,et al: "KN-62,a specific Ca^<++>/calmodulin-dependentprotein kinase inhibitopr,reversibly depress the rate of beating of cultured fetal mouse cardiac myocytes." J.Pharmacol.Exp.Ther.270. 1319-1324 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Serizawa,et al: "Immediate-early gene induction and MAP kinase activation during recovery from metabolic inhibition in cultured cardiac myocytes." J.Clin.Invest.(in press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamashita,et al: "Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning." J.Clin.Invest. (in press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Otsu,et al: "Sodium Dependence of the Na^+-H^+ Exchanger in the Pre-steady State" J.Biol.Chem.268. 3184-3193 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Otsu,et al: "Chromosome Mapping of Five Human Cardiac and Skeletal Muscle Sarcoplasmic Reticulum Protein Genes" Genomics. 17. 507-509 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kuzuya,et al: "Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia" Circ.Res.72. 1293-1299 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hoshida,et al: "Sublethal ischemia alters myocardial antioxidant activity in canine heart" Am.J.Physiol. 264. H33-H39 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Toyofuku,et al: "Amino Acids Glu^2 to Ile^<18> in the Cytoplasmic Domain of Phospholamban Are Essential for Functional Association with the Ca^<2+>-ATPase of Sarcoplasmic Reticulum" J.Biol.Chem.269. 3088-3094 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Otsu,et al: "The Point Mutation,Arg^<615> to Cys,in the Ca^<2+> Release Channel of Skeletal Sarcoplasmic Reticulum Is Responsible for Hypersensitivity to Caffeine and Halothane in Malignant Hyperthermia" J.Biol.Chem.269 (in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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