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

The role of ER stress and ubiquitin-proteasome system in the development of heart failrue

Research Project

Project/Area Number 17590731
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

MINAMINO Tetsuo  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30379234)

Co-Investigator(Kenkyū-buntansha) TAKASHIMA Seiji  Osaka University, Health care Center, Assistant, 保健センター, 助手 (90379272)
HORI Masatsugu  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20124779)
KITAKAZE Masafumi  National Cardiovascular Center, Department of Cardiovascular Medicine, Director, 生理機能検査部, 部長(研究職) (20294069)
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: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsubiquitin / proteasome / heart failure / apoptosis / ER stress
Research Abstract

The endoplasmic reticulum (ER) is recognized as an organelle that participates in folding secretory and membrane proteins. The ER responds to stress by upregulating ER chaperones, but prolonged and/or excess ER stress leads to apoptosis. However, the potential role of ER stress in pathophysiological hearts remains unclear. Cardiac expression of ER chaperones was significantly increased 1 and 4 weeks after transverse aortic constriction (TAC), indicating that pressure overload by TAC induced prolonged ER stress. The CHOP-, but not JNK-or caspase-12-, dependent pathway was activated in failing hearts by TAC. Finally, mRNA levels of ER chaperones were markedly increased in failing hearts of patients. These findings suggest that pressure overload by TAC induces prolonged ER stress, which may contribute to cardiac myocyte apoptosis during progression from cardiac hypertrophy to failure. The ubiquitin-proteasome (U/P) system contributes to regulation of apoptosis degrading apoptosis-regulato … More ry proteins. Marked accumulation of ubiquitinated proteins in cardiomyocytes of human failing hearts suggested impaired U/P system in heart failure. Since cardiomyocyte apoptosis contributes to the progression of cardiac dysfunction in pressure-overloaded hearts, we investigated the role of U/P system in such conditions. Proteasome activities already depressed before the onset of cardiac dysfunction in pressure-overloaded hearts of mice. Cardiomyocyte apoptosis was observed along with depression of proteasome activities and elevation of proapoptotic/antiapoptotic protein ratio in failing hearts. In cultured cardiomyocytes, pharmacological inhibition of proteasome accumulated proapoptotic proteins such as p53 and Bax. Gene silencing of these proapoptotic proteins by RNA interference prevented the accumulation of respective proteins and attenuated cardiomyocyte apoptosis induced by proteasome inhibition. We conclude that depression of proteasome activities contributes to cardiac dysfunction resulting from cardiomyocyte apoptosis through accumulation of proapoptotic proteins by impaired degradation. We are now checking the interaction between ER stress and ubiquitin-proteasome system in failing hearts. Less

Report

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

    (21 results)

All 2007 2006 2005

All Journal Article (17 results) Book (1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts.2007

    • Author(s)
      Asanuma H, Nakai K. 他
    • Journal Title

      J Mol Cell Cardiol. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prolonged Transient Acidosis During Early Reperfusion Contributes to the Cardioprotective Effects of Postconditioning.2007

    • Author(s)
      Fujita M, Asanum, 他
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Pages: 2004-2008

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts.2007

    • Author(s)
      Asanuma H, Nakai K, Sanada S, Minamino T, Takashima S, Ogita H, Fujita M, Hirata A, Wakeno M, Takahama H, Kim J, Asakura M, Sakuma I, Kitabatake A, Hori M, Komamura K, Kitakaze M.
    • Journal Title

      J Mol Cell Cardiol. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning.2007

    • Author(s)
      Fujita M, Asanuma H, Hirata A, Wakeno M, Takahama H, Sasaki H, Kim J, Takashima S, Tsukamoto O, Minamino T, Shinozaki Y, Tomoike H, Hori M, Kitakaze M.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 292(4)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-term stimulation of adenosine A2b receptors begun after myocardial infarction prevents cardiac remodeling in rats.2006

    • Author(s)
      Wakeno M, Minamino T, 他
    • Journal Title

      Circulation 114(18)

      Pages: 1923-1932

    • 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] Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs2006

    • Author(s)
      Hirata A, Minamino T, 他
    • Journal Title

      J Am Coll Cardiol. 48(1)

      Pages: 176-184

    • 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] Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition2006

    • Author(s)
      Okazaki H, Minamino T, 他
    • Journal Title

      Hypertens Res 29(4)

      Pages: 277-284

    • NAID

      10017985662

    • 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] Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs2006

    • Author(s)
      Asanuma H, Minamino T, 他
    • Journal Title

      J Mol Cell Cardiol 40(5)

      Pages: 666-674

    • 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] Long-term stimulation of adenosine Alb receptors begun after myocardial infarction prevents cardiac remodeling in rats.2006

    • Author(s)
      Wakeno M, Minamino T, Seguchi O, Okazaki H, Tsukamoto O, Okada K, Hirata A, Fujita M, Asanuma H, Kim J, Komamura K, Takashima S, Mochizuki N, Kitakaze M.
    • Journal Title

      Circulation. 114(18)

      Pages: 1923-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs.2006

    • Author(s)
      Hirata A, Minamino T, Asanuma H, Fujita M, Wakeno M, Myoishi M, Tsukamoto O, Okada K, Koyama H, Komamura K, Takashima S, Shinozaki Y, Mori H, Shiraga M, Kitakaze M, Hori M.
    • Journal Title

      J Am Coll Cardiol. 48(1)

      Pages: 176-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition.2006

    • Author(s)
      Okazaki H, Minamino T, Tsukamoto O, Kim J, Okada K, Myoishi M, Wakeno M, Takashima S, Mochizuki N, Kitakaze M.
    • Journal Title

      Hypertens Res. 29(4)

      Pages: 277-84

    • NAID

      10017985662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs.2006

    • Author(s)
      Asanuma H, Minamino T, Ogai A, Kim J, Asakura M, Komamura K, Sanada S, Fujita M, Hirata A, Wakeno M, Tsukamoto O, Shinozaki Y, Myoishi M, Takashima S, Tomoike H, Kitakaze M.
    • Journal Title

      J Mol Cell Cardiol. 40(5)

      Pages: 666-74

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ablation of MEK kinase 1 suppresses intimal hyperplasia by impairing smooth muscle cell migration and urokinase plasminogen activator expression in a mouse blood-flow cessation model.2005

    • Author(s)
      Li Yan
    • Journal Title

      Circulation 111

      Pages: 1672-1678

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aldosterone nongenomically worsens ischemia via protein kinase C-dependent pathways in hypoperfused canine hearts.2005

    • Author(s)
      Fujita Masashi
    • Journal Title

      Hypertension 46

      Pages: 113-117

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A calcium channel blocker amlodipine ircreases coronary blood flow via both adenosine- and NO-dependent mechanisms in ischemic hearts.2005

    • Author(s)
      Asanuma Hiroshi
    • Journal Title

      J Mol Cell Cardiol 39

      Pages: 605-614

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A role of opening of mitochondrial ATP-sensitive potassium channels in the infarct size-limiting effect of ischemic preconditioning via activation of protein kinase C in the canine heart.2005

    • Author(s)
      Tsukamoto Osamu
    • Journal Title

      Biochem Biophys Res Commun 338

      Pages: 1460-1466

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Depression of proteasome activities during the progression of cardiac dysfunction in pressure-overloaded heart of mice.2005

    • Author(s)
      Tukamoto Osamu
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 1125-1133

    • Related Report
      2005 Annual Research Report
  • [Book] Annual Review 循環器2007

    • Author(s)
      南野哲男
    • Total Pages
      6
    • Publisher
      小胞体ストレス
    • 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
  • [Patent(Industrial Property Rights)] METHOD FOR DIAGNOSING HEART FAILURE2006

    • Inventor(s)
      Tetsuo, Minamino et al.
    • Industrial Property Rights Holder
      Osaka University
    • Filing Date
      2006-08-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] METHOD FOR DIAGNOSING HEART FAILURE2006

    • Inventor(s)
      Tetsuo Minamino et al.
    • Industrial Property Rights Holder
      Osaka University
    • Filing Date
      2006-08-10
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 心不全の判定方法2006

    • Inventor(s)
      南野 哲男, 堀 正二, 岡田 健一郎, 北風 政史
    • Industrial Property Rights Holder
      国立大学法人大阪大学, 財団法人ヒューマンサイエンス振興財団
    • Industrial Property Number
      2006-016514
    • Filing Date
      2006-01-25
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi