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The role of anti-oxidant enzyme in cardioprotective effects of exercise and heat stress

Research Project

Project/Area Number 11470162
Research Category

Grant-in-Aid for Scientific Research (B).

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

Principal Investigator

KUZUYA Tsunehiko  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (80150340)

Co-Investigator(Kenkyū-buntansha) NISHIDA Masashi  Kobe College, Professor, 人間科学部・人間科学科, 教授 (40283783)
MASUYAMA Tohru  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70273670)
SATO Hideyuki  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70167435)
OTSU Kinya  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20294051)
山下 宣繁  大阪大学, 医学部・付属病院, 医員
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥12,200,000 (Direct Cost: ¥12,200,000)
KeywordsMn-SOD / TNF / IL / ischemia-reperfusion / oxygen radicals / exercise / Cardioprotective therapy / 運動療法 / 虚血耐性 / プレコンディショニング
Research Abstract

Oxygen radical, which is synthesized during cardiac ischemia-reperfusion, has been found to be a potential mediater for cardiac cell injury. To protect the ischemia-reperfusion injury, some approach to eliminate the production of oxygen radical has been tried. On the basis of the beneficial effects of exercise on the cardioprotection against various stresses including ischemia-reperfusion, we aimed to determine whether exercise induces some anti-oxidant effect in the heart.
(1) Mechanism of Mn-SOD induction by exercise
After rats were trained to exercise in the wheel, trained rats were sacrified and hearts were subjected to the biochemical analysis. Production of super-oxide, measured by using Dichrolofluorescein, was increased. MRNA and protein levels of TNF and IL were also increased. When rats were treated with TNF, IL, or H2O2, Mn-SOD was increased at both mRNA, protein, and activities.
(2) Induction of Mn-SOD in vascular system
On the basis of our result that stress-induced Mn-SOD has beneficial effects on heart, we further examined the Mn-SOD induction of vascular smooth muscle cells in response to ischemia. Ischemic stress also increased Mn-SOD at mRNA and activity. Smooth muscle cells over-expressing Mn-SOD could be resistant to the ischemic stress.
In conclusion, we determined that exercise induces Mn-SOD in virtue of the production of TNF and IL, leading to the anti-oxidant effects on the heart.

Report

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

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kitakaze M, Takashima S, Minamino T, Node K, Shinozaki Y, Mori H, Kuzuya T, Hori M: "Improvement by 5-Amino-4-imidazole carboxamide riboside of the contractile dysfunction that follows brief periods of ischemia through increases in ecto-5'-nucleotidase activity and adenosine release in canine hearts."Japanese Circulation Journal. 63. 542-553 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitakaze M, Sakata Y, Kodama K, Kuzuya T, Hori M: "Role of K_<ATP> channels in cardioprotection"Current Topics in Membranes. 46. 435-448 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hoshida S, Yamashita N, Kuzuya T, Hori M: "Differential effects of long-term renin-angiotensin system blockade on limitation of infarct size in cholesterol-fed rabbits."Atherosclerosis. 149. 287-294 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitakaze M, Asanuma H, Takashima S, Minamino T, Ueda Y, Sakata Y, Asakura M, Sanada S, Kuzuya T, Hori M: "Nifedioine-induced coronary vasodilation in ischemic hearts is attrible to bradykinin and NO-dependent mechanisms in dogs."Circulation. 101. 311-317 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Minamino T, Kitakaze M, Ueda Y, Asanuma H, Papst P.J, Kuzuya T, Terada N, Hori M: "Chronic Treatment with FK506 Increase p70 S6 Kinase Activity associated with Reduced Nitric Oxide Sybthase Activity in Rabbit Hearts"Cardiovascular Drugs and Therapy. 14. 329-336 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Minamino T, Kitakaze M, Papst P.J, Ueda Y, Sakata Y, Asanuma H, Ogai A, Kuzuya T, Terada N, Hori M: "Inhibition of Nitric Oxide Synthesis Induces Coronary Vascular Remodeling and Cardiac Hypertrophy Associated with the Activation of p70 S6 Kinase in Rats."Cardiovascular Drugs and Therapy. 14. 533-542 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masafumi Kitakaze: "Improvement by 5-Amino-4-imidazole carboxamide riboside of the contractile dysfunction that follows brief periods of ischemia through increases in ecto-5'-nucleotidase activity and adenosine release in canine hearts."Japanese Circulation. 63. 542-553 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masafumi Kitakaze: "Role of K_<ATP> channels in cardioprotection"Current Topics in Membranes. 46. 435-448 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shiro Hoshida: "Differential effects of long-term renin-angiotensin system blockade on limitation of infarct size in cholesterol-fed rabbits."Atherosclerosis. 149. 287-294 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masafumi Kitakaze: "Nifedioine-induced coronary vasodilation in ischemic hearts is attrible to bradykinin and NO-dependent mechanisms in dogs."Circulation. 101. 311-317 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tetsuo Minamino: "Chronic Treatment with FK506 Increase p70 S6 Kinase Activity associated with Reduced Nitric Oxide Sybthase Activity in Rabbit Hearts"Cardiovascular Drugs and Therapy. 14. 329-336 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tetsuo Minamino: "Inhibition of Nitric Oxide Synthesis Induces Coronary Vascular Remodeling and Cardiac Hypertrophy Associated with the Activation of p70 S6 Kinase in Rats."Cardiovascular Drugs and Therapy. 14. 533-542 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamashita N et al.: "Exercise provides direct biphasic cardioprotecition via manganese superoxide dismutase activation"J Exp Med. 189. 1699-1706 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamashita N et al.: "Monophosphory lipic A provides biphasic cardioprotection against ischemia-reperfusioninjury in rat hearts"Br J Pharmacol. 128. 412-418 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwakura K et al.: "Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the no-reflow phenomenon"Am J Cardiol. 84. 415-419 (1999)

    • Related Report
      1999 Annual Research Report

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

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