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Treatment of heart failure by modulating Ca signaling protein gene expression

Research Project

Project/Area Number 10670648
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OTSU Kinya  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20294051)

Co-Investigator(Kenkyū-buntansha) TOYOFUKU Toshihiko  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手
MATSUMURA Yasushi  Osaka University Hospital, Associate Professor, 医学部・附属病院, 助教授 (90252642)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCa / Ca release channel / calpain / Sarcoplasmic reticulum / gene expression / コネクシン / Caシグナリング / 筋小胞体 / Ca遊離チャネル / 心不全
Research Abstract

Cardiac contractility is regulated by intracellular calcium concentration. Sarcoplasmic reticulum (SR) plays a major role for the regulation of intracellular calcium concentration. Ca release from SR through Ca release channel of SR induces muscle contruction, whereas Ca uptake by CaATPase of SR leads to muscle relaxation. In cardiac hypertrophy and heart failure, the expression of the Ca signaling proteins of SR have been reported to be altered. This changes in the expression of SR genes may be a cause for cardiac dysfunction and normalization of the changes in gene expression could be a novel treatment for heart failure. In this study, we attempted to elucidate a molecular mechanism for gene regulation of SR proteins, especially Ca release channel. We isolated 5'upstream region of the gene and ligated to lufiferase expression vector. We measured the luciferase activity in cardiac and skeletal muscle cells. The promotor of the gene is not tissure-specific. We found a region which suppresses the expression of the channel in skeletal muscle. This region contains E-box sequence. Gel shift assay indicated a novel bHLH protein binds to the region and regulates the expression.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Toshihiko Toyofuku: "Intracellular Calcium Signaling via Gap Junction in Connexin-43-transfected Cells"Journal of Biological Chemistry. 273. 1519-1528 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Direct Association of the Gap Junction Protein Connexin-43 with ZO-1"Journal of Biological Chemistry. 273. 127275-12731 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masanori Yabuki: "Involvement of NF-Y in transcriptional regulation of the phospholamban gene"European Journal of Biochemistry. 258. 744-751 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Functional role of c-Src in gap junctions of the cardiomyopathic heart"Circulation Reseaech. 85. 672-681 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motoo Date: "Single Strand Conformation Polymorphism Analysis on the δ-sarcoglycan Gene in Japanese Patients with Hypertrophic Cardiomyopathy"American Journal of Cardiology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Intercellular signaling via gap junction in connexin-43-transfected cells."J. Biol. Chem. 273. 1519-1528 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes."J. Biol. Chem. 273. 12725-12731 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masanori Yabuki: "Involvement of NF-Y in transcriptional regulation of the phospholamban gene."Eur. J. Biochem. 258. 744-751 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Functional role of c-Src in gap junctions of the cardiomyopathic heart."Circ. Res.. 85. 672-681 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moto-o Date: "Single Strand Conformation Polymorphism Analysis on the delta-sarcoglycan Gene in Japanese Patients with Hypertrophic Cardiomyopathy."Am. J. Cardiol.. (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshihiko Toyofuku: "Functional role of c-Src in gap junctions of the cardiomyopathic heart"Circulation.Research. 85. 672-681 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Motoo Date: "Single Strand Conformation Polymorphism Analysis on the δ-sarcoglycan Gene in Japanese Patients with Hypertrophic Cardiomyopathy"American Journal of Cardiology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Yabuki M,et al.: "Involvement of NF-Y in transcriptional regulation of the phospholamban gene." Eur.J.Biochem.258. 744-751 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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