• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis and Clinical Application of essential signaling pathway in cardiomyocyte

Research Project

Project/Area Number 14570660
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

HIROTA Hisao  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30273684)

Co-Investigator(Kenkyū-buntansha) TAKIHARA Keiko  Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (70252640)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordscardiomyocyte / smad1 / gab1 / apoptosis / bcl-xL / bone morphogeetic protein / Stat3
Research Abstract

1.To examine whether Smad1 activates and plays a role during ischernia-reperfusion of heart in vivo, we generated cardiac-specific Smad1 TG mice by using the α-myosin heavy chain gene promoter. To examine whether Smad1 prevents injury of cardiomyocytes in vivo, we subjected Smad1 TG mice and wild-type mice to ischemia-reperfusion injury induced by 60 minutes of ligation of the left coronary artery and 60 minutes of reperfusion. Histological, TUNEL and DNA ladder analyses showed that Smad1 TG mice presented significantly smaller myocardial infarction and fewer apoptotic deaths of cardiomyocytes than the wild-type mice did. Interestingly, the increased expression of Bcl-xL was more remarkable, whereas caspase 3 was less activated, in the heart of Smad1 TG mice than that in the wild-type mice. These findings suggest that the Smad1 signaling pathway plays a role in cardioprotection against ischemia-reperfusion injury through the induction of Bcl-xL in vivo.
2. Gab1 (Grb2-associated binder-1 … More ), a scaffolding/docking protein, is tyrosine-phosphorylated and associates with protein tyrosine phosphatase SHP2 and p85 phosphatidylinositol 3-kinase upon stimulation with various cytokines and growth factors, including interleukin-6 and leukemia inhibitory factor. We constructed three kinds of adenovirus vectors carrying wild-type Gab1 (AdGab1^<WT>) mutated Gab1 lacking SHP2 binding site (AdGab1^<F627/659>) and β-galactosidase (Adβ-gal). Compared with cardiomyocytes infected with Adb-gal, longitudinal elongation of cardiornyocytes induced by LIE was enhanced in cardiomyocytes infected with AdGab1^<WT> but inhibited in cardiomyocytes infected with AdGab1^<F627/659> Furthermore, activation of extracellular signal-regulated kinase 5 (ERK5) was enhanced in cardiomyocytes infected with AdGab1^<WT> compared with cardiomyocytes infected with Adj3-gal, but repressed in cardiomyocytes infected with AdGab1^<F627/659>. Co-infection of AdGab1^<WT> with adenovirus vector carrying dominant-negative ERK5 abrogated longitudinal elongation of cardiomyocytes induced by LIE. Taken together, these findings indicate that Gabl-SHP2 interaction plays a crucial role in gp13O-dependent longitudinal elongation of cardiomyoctes through activation of ERK5. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Nagai H et al.: "A case of specific cardiomyopathy caused by multisystemic lipid storage in Jordans' anomaly."Int Med. 42. 587-590 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaoka Y et al.: "Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaff olding/Docking Protein Gab1 with Tyrosine Phosphatase SHP2 in Cardiomyocytes."Circ Res. 93. 221-229 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugiyama S et al.: "Novel Insertional Mutation in the Bone Morphogenetic Protein Receptor type II Associated with Sporadic Primary Pulmonary Hypertension."Cric J. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki M et al.: "Solitary Right Ventricle Metastasis by Renal Cell Carcinoma"J AM SOC ECHOCARDIOG. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirota H et al.: "Circulating Interlenkin-6 Family Cytokines and their Receptors in Patients with Congestive Heart Failure"Heart Vessels. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirota H et al.: "Kluwer Academic Publishers"SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STATs) ACTIVATION AND BIOLOGY, CHAPTER 44 STATs in Cardiovascular System.. 746 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai H et al.: "A case of specific cardiomyopathy caused by multisystemic lipid storage in Jordans' anomaly."Int Med.. 42. 587-590 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaoka Y et al.: "Activation of gp13O Transduces Hypertrophic Signal Through Interaction of Scaff olding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in Cardiomyocytes."Circ Res.. 93. 221-229 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugiyama S et al.: "Novel Insertional Mutation in the Bone Morphogenetic Protein Receptor type II Associated with Sporadic Primary Pulmonary Hypertension."Circ J.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki M et al.: "Solitary Right Ventricle Metastasis by Renal Cell Carcinoma."J AM SOC ECHOCARDIOG.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirota H et al.: "Circulating Interlenkin-6 Family Cytokines and their Receptors in Patients with Congestive Heart Failure."Heart Vessels.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirota H et al.: "SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STATS) ACTIVATION AND BIOLOGY, CHAPTER 44 STATs in Cardiovascular System."Kluwer Academic Publishers.. 746 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai H et al.: "A case of specific cardiomyopathy caused by multisystemic lipid storage in Jordans' anomaly"Int Med. 42. 587-590 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakaoka Y et al.: "Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaff olding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in Cardiomyocytes"Circ Res. 93. 221-229 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugiyama S et al.: "Novel Insertional Mutation in the Bone Morphogenetic Protein Receptor type II Associated with Sporadic Primary Pulmonary Hypertension"Circ J. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaki M et al.: "Solitary Right Ventricle Metastasis by Renal Cell Carcinoma"J AM SOC ECHOCARDIOG. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirota H et al.: "Circulating Interlenkin-6 Family Cytokines and their Receptors in Patients with Congestive Heart Failure"Heart Vessels. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirota H et al.: "Kluwer Academic Publishers"SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STATs) ACTIVATION AND BIOLOGY, CHAPTER 44 STATs in Cardiovascular System. 746 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osugi T et al.: "Cardiac-specific activation of signal transducer and activator of transcription 3 promotes vascular formation in the heart"J Biol Chem. 277・8. 6676-6681 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kunisada K et al.: "Bcl-xl reduces doxorubicin-induced myocardial damage but fails to control cardiac gene downregulation"Cardiovasc Res. 53・4. 936-943 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oshima Y et al.: "Specific cardiomyopathy caused by multisystemic lipid storage in Jordan's anomaly"Circulation. 9. 280-281 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugiyama S et al.: "Novel Insertional Mutation in the Bone Morphogenetic Protein Receptor type II Associated with Sporadic Primary Pulmonary Hypertension"Circulation Journal. (in press).

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi