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Role of signal transduction mediated by diacylglycerol and phosphatidic acid in cardiac hypertrophy

Research Project

Project/Area Number 17590699
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KAGAYA Yutaka  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (90250779)

Co-Investigator(Kenkyū-buntansha) GOTO Kaoru  Yamagata University, School of Medicine, Professor, 医学部, 教授 (30234975)
KARIBE Akihiko  Tohoku University, Hospital, Research Associate, 病院・助手 (80359504)
武田 守彦  東北大学, 病院・医員 (30375084)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsSignal transduction / Cardiac hypertrophy / Cardiac failure / Diacylglycerol / Phsphatidic acid / ジアシルグリセロールキナーゼ / プロテインキナーゼC
Research Abstract

Protein kinase C that is activated by 1, 2-diacylglycerol (DG) plays an important role in the development of cardiac hypertrophy. Amount of DG in myocardium is regulated by DG kinase (DGK) as well as by phosphatidic acid phosphatase. We for the first time reported that DGK ε and DGK ζ are predominant isozymes that express in normal rat myocardium and that both isozymes play distinct roles in the process of ventricular remodeling after myocardial infarction.
At 28 days after operations, expression levels of DGK ε mRNA but not DGK ζ in left-ventricular myocardium significantly decreased in aortic-banded rats as compared with sham-operated rats. DGK ζ protein in the myocardium translocated from the particulate to the cytosolic compartment in aortic-banded rats. Furthermore, myocardial content of DG and PKCδ protein expression in the particulate fraction of the myocardium significantly increased in aortic-banded rats compared with sham-operated rats. These results suggest that DGK ε and DGK ζ play distinct roles in the development of pressure overload-induced cardiac hypertrophy and that the two isozymes are differentially regulated.
In transgenic mice with cardiac-specific overexpression of DGK ζ, extent of cardiac hypertrophy induced by aortic constriction did not differ from that in wild-type mice. This was also the case with pressure overload induced by continuous angiotensin II infusion. These findings are not consistent with those in the rat model of pressure overload-induced cardiac hypertrophy. On possible reason for the inconsistent results may be relatively low expression levels of the transgene of DGK ζ, in our transgenic model. A further study is required to solve this issue.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report

Research Products

(17 results)

All 2007 2006 2005

All Journal Article (16 results) Book (1 results)

  • [Journal Article] Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats2007

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

      Acta Physiol 189

      Pages: 221-231

    • 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] Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice2007

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

      Circ Res 100

      Pages: 662-669

    • 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] Protective role of endogenous erythropoietin system in non-hematopoietic cells against pressure overload-induced left ventricular dysfunction in mice2007

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

      Circulation 115

      Pages: 2022-2032

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats.2007

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

      Acta Physiol. 189

      Pages: 221-231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats2007

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

      Circ Res. 100

      Pages: 662-669

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Protective role of endogenous erythropoietin system in non-hematopoietic cells against pressure overload-induced left ventricular dysfunction in mice2007

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

      Circulation. 115

      Pages: 2022-2032

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Protective role of endogenous erythropoietin system in non-hematopoietic cells against pressure overload-induced left ventricular dysfunction in mice2007

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

      Circulation (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion2006

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

      Cardiovasc Res 71

      Pages: 466-477

    • 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] Effect of nifekalant in failing hearts in rats2006

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

      J Pharmacol Exp Ther 318

      Pages: 1102-1107

    • 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] Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion.2006

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

      Cardiovasc Res. 71

      Pages: 466-477

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of nifekalant in failing hearts in rats.2006

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

      J Pharmacol Exp Then 318

      Pages: 1102-1107

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Important role of endogenous erythropoietin system to recruit endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice2006

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

      Circulation (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention2005

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

      J Am Coll Cardiol 45

      Pages: 1406-1412

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Myocardial [C-11] labeled diacylglycerol accumulation and left ventricular remodeling in post myocardial infarction patients2005

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

      J Nucl Med 46

      Pages: 553-559

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differential regulation of diacylglycerol kinase isozymes in cardiac hypertrophy2005

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

      Biochem Biophys Res Commun 332

      Pages: 101-108

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased [^<18>F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol2005

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

      J Am Coll Cardiol 45

      Pages: 1849-1855

    • Related Report
      2005 Annual Research Report
  • [Book] 分子イメージングの将来展望2005-私の考え方・取り組み方-(石田良雄編)2005

    • Author(s)
      加賀谷 豊(共著)
    • Total Pages
      48
    • Publisher
      日本心臓核医学会
    • Related Report
      2005 Annual Research Report

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Published: 2005-03-31   Modified: 2016-04-21  

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