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Analysis of functional significance of mutant actin identified in hereditary dilated cardiomyopathy

Research Project

Project/Area Number 11670661
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

SUGIURA Seiryo  University of Tokyo, Facuulty of Medicine Assistant, 医学部・附属病院, 助手 (10272551)

Co-Investigator(Kenkyū-buntansha) FUJITA Hideo  University of Tokyo, Facuulty of Medicine Assistant, 医学部・附属病院, 助手
YAMASHITA Hiroshi  University of Tokyo, Facuulty of Medicine Assistant, 医学部・附属病院, 助手 (50323572)
AOYAGI Teruhiko  University of Tokyo, Facuulty of Medicine Assistant, 医学部・附属病院, 助手 (10251240)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsActin / myosin light chain / in vitro motility assay / 拡張型心筋症 / インビトロアッセイ
Research Abstract

In this study, we evaluated the functional significance of cardiac actin focussing on its interaction with myosin ligh chain. We compared the atrial and ventricular types of cardiac myosin obtained from rat heart which are known to differ only in light chain structure. Although acitn-activated ATPase activity did not differ between the two myosins atrial type myosin showed higher actin sliding velocity in vitro. Force generating ability in vitro, however, was highe for ventricular type myosin. Single molecular measurement of force suggested the distinct kinetics of actin-myosin interaction of these myosins. We concluded that the heavy chain structure of myosin determines the catalytic activity and that the light chains are modifiers of its kinetics. To further elucidate the mechanism of this modification, we studied the effect of N-terminus peptide of essentila light chain on contractile function of cardiac myocyte. N-terminu peptide enhanced the contractility supporting the hypothesis of tethering effect of this peptide. We also developed novel experimental set up for measuring the fwitch force developed by a single cardiac mnyocyle.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Aoyagi T: "The sarcoplasmic reticulum Ca2+-ATPase (SERCA2)gene promoter activity is decrease response to severe left ventricular pressure-overload hypertrophy in rat hearts."J Mol Cell Cardiol. 31. 919-926 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugiura S: "Actin myosin interaction"Cardiovasc Res. 44. 266-273 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyaji K,: "Myocardial tactile stiffness during acute reduction of coronary blood flow."Ann Thorac Surg. 69. 151-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sata M,: "Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cGMP independent mechanism."Hypertension. 36. 83-88 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eto Y,: "Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training."Circulation. 101. 2134-2137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yonekura K,: "Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasminc reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction."Bas Res Cardiol. 95. 343-348 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyagi T, Yonekura K, Eto Y, Matsumoto A, Yokoyama I, Sugiura S, Momomura S, Hirata Y, Baker DL, Periasamy M: "The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene promoter activity is decreased in response to severe left ventricular pressture-overload hypertrophy in rat hearts."J Mol Cell Cardiol. 31. 919-926 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugiura S: "Actin myosin interaction"Cardiovasc Res. 44. 266-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyaji K, Sugiura S, Inaba H, Takamoto S, Omata S: "Myocardial tactile stiffness during acute reduction of coronary blood flow."Ann Thorac Surg. 69. 151-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sata M, Kakoki M, Nagata D, Nishimatsu H, Suzuki E, Aoyagi T, Sugiura S, Kojima H, Nagano T, Kangawa K, Matsuo H, Omata M, Nagai R, Hirata Y: "Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cGMP-independent mechanism."Hypertension. 36. 83-88 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eto Y, Yonekura K, Sonoda M, Arai N, Sata M, Sugiura S, Takenaka K, Gualberto A, Hixon M.L., Wagner M.W., Aoyagi T: "Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training."Circulation. 101. 2134-2137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yonekura K,_Eto Y,Yokoyama I,Matsumoto A, Sugiura S, Momomura S, Kirimoto T, Hayashi Y, Omata M, Aoyagi T.: "Inhibition of camitine synthesis modulates protein contents of the cardiac sarcoplasminc reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction."Bas Res Cardiol. 95. 343-348 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yonekura K,: "Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasminc reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction."Bas Res Cardiol. 95. 343-348 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aoyagi T: "The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene promoter activity is decreased in response to severe left ventricular pressure-overload hypertrophy in rat hearts."J Mol Cell Cardiol. 31. 919-926 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugiura S: "Actin myosin interaction"Cardiovasc Res. 44. 266-273 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyaji K,: "Myocardial tactile stiffness during acute reduction of coronary blood flow."Ann Thorac Surg. 69. 151-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sata M,: "Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cGMP-independent mechanism."Hypertension. 36. 83-88 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eto Y,: "Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training."Circulation. 101. 2134-2137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugiura S: "Actin-myosin intraction"Cardiovascular Research. 44. 266-273 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aoyagi T: "The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene promoter activity is decreased in response to severe left ventricular pressure-overload hypertrophy in rar hearts"J Mol Cell Cardiol. 31. 919-926 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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