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Inhibition for the Low Flow Hypoxia-Induced Mitochondrial Dysfunction using Methylprednisolone and Bcl-2

Research Project

Project/Area Number 13671213
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionAkita University

Principal Investigator

MOTOYAMA Satoru  Akita Universify, School of Medicine, Lecturer, 医学部, 講師 (60292372)

Co-Investigator(Kenkyū-buntansha) SAITO Reijiro  Akita University, School of Medicine, Lecturer, 医学部, 講師 (90272038)
MINAMIYA Yoshiro  Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (30239321)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Keywordsischemic liver / apoptosis / hydrogen peroxide / glucocorticoid / mitochondria / Bcl-2 / sinusoidal enddothelial cell / 虚血 / メチルプレドニゾロン
Research Abstract

1 Bcl-2 localization
Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. We report that Bcl-2 is expressed in normal rat liver, and located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.
2 The hypoxia-induced mitochondrial Bcl-2 decline
The apoptotic nonparenchymal cells, identified as SECs, were observed, predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchyma! ceils were stained. Mitochondrial Bcl-2 levels declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. Pretreatment with a specific xanthine oxidase inhibitor blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.
3 The mechanism by which methyiprednisolone protects the ischermic liver
Pretreatment with 30 mg/kg, 10mg/kg or 3 mg/kg methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization, and enzyme leakage, though hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. The beneficial effect of methylprednisolone appears to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Satoru Motoyarna, et al.: "Methylprednisolone Inhibits Low Flow Hypoxia-Induced Mitochondrial Dysfunction in Isolated Perfused Rat Liver"Crit Care Med. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama, et al.: "Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver"J Surg Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama, et al.: "Mitochondrial Ubiquinone (Coenzyme Q1O) : Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Prominent Press, Ed.Ebadi M, Marwash J, Chopra RK.. 550 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama.: "Methylprednisolone Inhibits Low Flow Hypoxia-Induced Mitochondrial Dysfunction in Isolated Perfused Rat Liver"Crit Care Med. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama: "Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver."J Surg Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama, Ed. EbadiM, Marwash J, Chopra PK: "Mitochondrial Ubiquinone (Coenzyme Q10): Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Prominent Press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoru Motoyama, et al.: "Methylprednisolone Inhibits Low Flow Hypoxia-Induced Mitochondrial Dysfunction in Isolated Perfused Rat Liver"Crit.Care Med.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoru Motoyama, et al.: "Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver"J.Surg.Res.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Motoyama S et al.: "Mitochondrial Ubiquinone (Co enzyme Q10) : Biochemical, Functional, medical, and Therapeutic Aspect in Human Health and Disease"Ebadi M, Marwash J, Chopra RK Ed Prominent Press. 998 (2001)

    • Related Report
      2001 Annual Research Report

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

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