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Protective mechanisms of skeletal muscle against oxidative stress by physical exercise: the role of uncoupling protein via NO

Research Project

Project/Area Number 15300223
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Sports science
Research InstitutionKyorin University

Principal Investigator

OHNO Hideki  Kyorin University, School of Medicine, Professor, 医学部, 教授 (00133819)

Co-Investigator(Kenkyū-buntansha) KIZAKI Takako  Kyorin University, School of Medicine, Associate Professor, 医学部, 助教授 (00322446)
HITOMI Yoshiaki  Kanazawa University, Graduate School of Medical Science, Lecturer, 大学院・医学系研究科, 講師 (70231545)
中野 法彦  杏林大学, 医学部, 講師 (40322721)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥16,700,000 (Direct Cost: ¥16,700,000)
Fiscal Year 2004: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2003: ¥11,200,000 (Direct Cost: ¥11,200,000)
Keywordsexercise / skeletal muscle / leukocyte / superoxide dismutase / nitrogen oxide / nitric oxide synthase / uncoupling protein / oxidative stress
Research Abstract

Exercise is considered to serve as one of useful tools for the prevention and remedy against lifestyle-related diseases. On the other hand, physical exercise markedly enhances a flow of blood in skeletal muscle, thereby leading to an increase in the production of reactive oxygen species (ROS). In 2003 we demonstrated that the increased production of ROS by acute eccentric exercise in mouse skeletal muscle might be due to factors other than leukocytes, and that extracellular superoxide dismutase (EC-SOD) had a part in antiarteriosclerotic effects of exercise. Unexpectedly, there were no significant changes in uncoupling proteins (UCP2 and UCP3) or nitric oxide synthases (NOS-I, II, III) in skeletal muscle from mice after the exercise.
In 2004 we made a human study. The physical training executed consisted of 30-min interval training (swimming or running) in addition to 30-min long-distance training (swimming or running) per day, 5 times per week, during 3 months. Muscle biopsies were taken before and after the training. All the subjects notably increased their VO_2max levels, indicating an improvement in aerobic capacity. After training, there were significant decreases in the expression of mRNAs for HSP70, CuZn-SOD, and Mn-SOD but a significant increase in UCP2 mRNA expression, whereas no definite changes were observed in the levels of mRNAs for VEGF, bFGF, HIF1α, myoglobin, or UCP3. Moreover, the changes in HIF1α mRNA expression correlated well with those in VEGF mRNA expression after training. The increased expression of UCP2 mRNA might attenuate the generation of ROS during the training period. Taken together, it is envisioned that cumulative effects of transient changes in transcription during recovery from successive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with endurance training.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (34 results)

All 2005 2004 2003 Other

All Journal Article (24 results) Book (1 results) Patent(Industrial Property Rights) (2 results) Publications (7 results)

  • [Journal Article] Seven skeletal muscles rich in slow muscle fibers may function to sustain neutral position in the rodent hindlimb2005

    • Author(s)
      Hitomi, Y. et al.
    • Journal Title

      Comp.Biochem.Physiol.B 140・1

      Pages: 45-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Changes in nitric oxide and inducible nitric oxide synthase following stretch induced injury to the tibialis anterior muscle of rabbit2005

    • Author(s)
      Sakurai, T. et al.
    • Journal Title

      Jpn.J.Physiol. 55(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Seven skeletal muscles rich in slow muscle fibers may function to sustain neutral position in the rodent hindlimb.2005

    • Author(s)
      Hitomi, Y. et al.
    • Journal Title

      Comp.Biochem.Physiol.B 140(1)

      Pages: 45-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in nitric oxide and inducible nitric oxide synthase following stretch induced injury to the tibialis anterior muscle of rabbit.2005

    • Author(s)
      Sakurai, T. et al.
    • Journal Title

      Jpn.J.Physiol. 55(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Simple method for the identification of oxidative fibers in skeletal muscle2004

    • Author(s)
      Takemasa, T. et al.
    • Journal Title

      Eur.J.Appl.Physiol. 91・2-3

      Pages: 357-359

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm2004

    • Author(s)
      Itoh, M. et al.
    • Journal Title

      Am.J.Physiol.Regul.Integr.Comp.Physiol. 287・1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Down-regulation of β_2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation2004

    • Author(s)
      Itoh, C.E.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 322・3

      Pages: 979-984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acute exercise alters Gαi2 protein expressions through the ubiquitin-proteasome proteolysis pathway in rat adipocytes2004

    • Author(s)
      Ogasawara, J. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 323・3

      Pages: 1109-1115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Contribution of the calcineurin signaling pathway to overload-induced skeletal muscle fiber-type transition2004

    • Author(s)
      Miyazaki, M. et al.
    • Journal Title

      J.Physiol.Pharmacol. 55・4

      Pages: 751-764

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Wide use of merthiolate may cause mercury poisoning in Mexico.2004

    • Author(s)
      Ohno, H. et al.
    • Journal Title

      Bull.Environ.Contam.Toxicol. 73(5)

      Pages: 777-780

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Contribution of the calcineurin signaling pathway to overload-induced skeletal muscle fiber-type transition.2004

    • Author(s)
      Miyazaki, M. et al.
    • Journal Title

      J.Physiol.Pharmacol. 55(4)

      Pages: 751-764

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acute exercise alters Gαi2 protein expressions through the ubiquitin-proteasome proteolysis pathway in rat adipocytes.2004

    • Author(s)
      Ogasawara J. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 323(3)

      Pages: 1109-1115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Down-regulation of β_2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation.2004

    • Author(s)
      Itoh, C.E.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 322(3)

      Pages: 979-984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Supplementation of antioxidants prevents oxidative stress during a deep saturation dive.2004

    • Author(s)
      Ikeda, M. et al.
    • Journal Title

      Tohoku J.Exp.Med. 203(4)

      Pages: 353-357

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm.2004

    • Author(s)
      Itoh, M. et al.
    • Journal Title

      Am.J.Physiol.Regul.Integr.Comp.Physiol. 287(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Simple method for the identification of oxidative fibers in skeletal muscle.2004

    • Author(s)
      Takemasa, T. et al.
    • Journal Title

      Eur.J.Appl.Physiol. 91(2-3)

      Pages: 357-359

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm2004

    • Author(s)
      Itoh, M. et al.
    • Journal Title

      Am.J.Physiol.Regal.Integr.Comp.Physiol. 287・1

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Down-regulation of β_2-adrenergic receptor expression by exercise training increases IL-12 prodion by macrophages following LPS stimulation2004

    • Author(s)
      Itoh, C.E.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 322・3

      Pages: 979-984

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced expression of neuronal nitric oxide synthase in islets of exercise-trained rats.2003

    • Author(s)
      Ueda, H. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 312(3)

      Pages: 794-800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of moderate acute exercise on expression of mRNA involved in the calcineurin signaling pathway in human skeletal muscle.2003

    • Author(s)
      Hitomi, Y. et al.
    • Journal Title

      IUBMB Life 55(7)

      Pages: 409-413

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An inter-subunit disulfide bond affects affinity of human lung extracellular superoxide dismutase to heparin.2003

    • Author(s)
      Ookawara, T. et al.
    • Journal Title

      Free Radic.Res. 37(8)

      Pages: 823-827

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic variation in hypoxia-inducible factor 1α and its possible association with high altitude adaptation in Sherpas.2003

    • Author(s)
      Suzuki, K. et al.
    • Journal Title

      Med.Hypotheses 61(3)

      Pages: 385-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intermittent hypobaric hypoxia increases the ability of neutrophils to generate superoxide anion in humans.2003

    • Author(s)
      Hitomi, Y. et al.
    • Journal Title

      Clin.Exp.Pharmacol.Physiol. 30(9)

      Pages: 659-664

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of endurance training on three superoxide dismutase isoenzymes in human plasma.2003

    • Author(s)
      Ookawara, T. et al.
    • Journal Title

      Free Radic.Res. 37(7)

      Pages: 713-719

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 百寿者になろう-運動・栄養・休養のトライアングル-2004

    • Author(s)
      大野秀樹
    • Total Pages
      191
    • Publisher
      ナップ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 遺伝子導入促進剤およびそれを含む遺伝子導入用組成物2004

    • Inventor(s)
      人見 嘉哲, 大野 秀樹
    • Industrial Property Rights Holder
      人見 嘉哲, 大野 秀樹, (株)ジェー・ジー・エス
    • Filing Date
      2004-09-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 遺伝子導入促進剤およびそれを含む遺伝子導入用組成物2004

    • Inventor(s)
      人見 嘉哲, 大野 秀樹
    • Industrial Property Rights Holder
      人見 嘉哲, 大野 秀樹, (株)ジェー・ジー・エス
    • Filing Date
      2004-09-10
    • Related Report
      2004 Annual Research Report
  • [Publications] Ookawara, T.et al.: "Effects of endurance training on three superoxide dismutase isoenzymes in human plasma"Free Radic.Res.. 37・7. 713-719 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hitomi, Y.et al.: "Effect of moderate acute exercise on expression of mRNA involved in the calcineurin signaling pathway in human skeletal muscle"IUBMB Life. 55・7. 409-413 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ueda, H.et al.: "Enhanced expression of neuronal nitric oxide synthase in islets of exercise-trained rats"Biochem.Biophys.Res.Commun.. 312・3. 794-800 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohno, H.et al.: "Extracellular superoxide dismutase and lifestyle related diseases"Curr.Top.Pharmacol.. 8・1. 1-15 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takemasa, T.et al.: "Symple method for the identification of oxidative fibers in skeletal muscle"Eur.J.Appl.Physiol.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito, M.et al.: "The effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm"Am.J.Physiol.Regul.Integr.Comp.Physiol.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大野秀樹, 木崎節子: "健康スポーツ科学"文光堂. 295 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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