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Response in Myocytes and Change in Antioxidants Induced by Oxidative Stress

Research Project

Project/Area Number 09670421
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionKobe Gakuin University

Principal Investigator

OKAMOTO Tadashi  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (80194398)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Takayuki  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (40216726)
KISHI Takeo  Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70028843)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsUbiquinone / Maximal oxygen uptake / Cardiac myocytes / Antioxidants / Oxidative stress / Selenium / glutathione peroxidase / Ergometer / heart / selenium / glutathione / cultured cardiac myocytes / γ-glutamylcysteinylethyl ester / cell injury / oxidative stress / ubiquinone / coenzyme Q / 骨格筋 / 酸化的ストレス / 運動負荷 / 血清
Research Abstract

1)Decreased serum ubiquinol-lO levels in healthy subjects during exercise at maximal oxygen uptake
We studied the changes of serum ubiquinol-lO (UQH_2-1O, a reduced form of ubiquinone) levels during exercise on a bicycle ergometer at maximal oxygen uptake (VO_<max>) In response to the exercise, serum level of lactate at VO_<max> was S times higher than that before the exercise. Among serum antioxidants, the ratio of the UQH_2-1O to the total UQ-1O (UQH_2-1O/total UQ-1O (UQH_2-1O + UQ-1O)) at VO_<max> was significantly lower than that before the exercise. Serum levels of ascorbate but not alpha-tocopherol at VO_<max> were 1.2 times higher than those before the exercise.
This study demonstrated that in the response to aerobic exercise on a bicycle ergometer at VO_<max>, serum levels of UQH_2-1O and ascorbate changed, and also showed that such antioxidants may play beneficial role for the elimination of exercise-derived oxygen radicals.
2)Protective effect of gamma-glutamylcysteinylethyl ester on dysfunction of the selenium-deficient rat heart
Selenium (Se) deficiency induced a 62% incidence of electrocardiographic abnormalities, a 63% reduction in dP/dt in the left ventricle, and an increase in thiobarbituric acid reacting substances (TBARS). Administration of gamma-glutamylcysteinylethyl ester (gamma-GCE)(a membrane-permeating GSH precursor) increased the intracellular GSH concentration ([GSH]i) and prevented the cardiac dysfunction and the TBARS increment. The V*, but not the K_m, for GSH of Se-dependent GSH peroxidase (Se-Gpx) activity in Se-deficient rat heart homogenates was one-third that of normal rat heart homogenates. Although gamma -GCE did not affect the Se-Gpx V_<max> and K_m, forGSH, it did induce a substantial and significant increase in [GSH]_i.
These data suggest that the increase in [GSH]_i may have played a role in preventing the TBARS increase and cardiac dysfunction in Se-deficient rats.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] T.Kishi et al.: "Cytosolic NADPH-UQ reductase-linked recycling of cellular ubiquinol : its protective effect against carbon tetrachloride hepatotoxicity in rat" Molec.Aspects Med.18. S71-S77 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Okamoto et al.: "Protective effect of γ-glutamylcysteinylethyl ester on dysfunction of the selenium-deficient rat heart" Biochem.Pharmacol.57. 955-963 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Okamoto et al.: "Decreased serum ubiquinol-10 levels in healthy subjects during exercise at maximal oxygen uptake" BioFactors. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kishi et al.: "Cytosolic NADPH-UQ reductase-linked recycling of cellular ubiquinol : its protective effect against carbon tetrachloride hepatotoxicity in rat" Molec.Aspects Med.18. S71-S77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Okamoto et al.: "Protective effect of gamma-glutamylcysteinylethyl ester on dysfunction of the selenium-deficient rat heart" Biochem. Pharmacol. 57. 955-963 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Okamoto et al.: "Decreased serum ubiquinol-10 levels in healthy subjects during exercise at maximal oxygen uptake" BioFactors. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Okamoto et al.: "Protective effect of γ-glutamylcysteinylethyl ester on dysfunction of the selenium-deficient rat heart" Biochemical Pharmacology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeo Kishi: "Cytosolic NADPH-UQ Reductase-linked Recycling of Cellular Ubiquinol : Its Protective Effect against Carbon Tetrachloride Hepatotoxicity in Rat" Molec.Aspects Med.18. s71-s77 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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