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The Study of Heme Oxygenase Induction in the Hippocampus by Brain Ischemia and Hypoxia.

Research Project

Project/Area Number 10672162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

TANIGUCHI Takashi  Kyoto Pharm. Univ., Dept. of Neurobiology, Professor, 薬学部・病態生理学, 教授 (10111957)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsBrain ischemia / Hippocampus / Heme Oxygenase / Microglia / Astrocyte / Oxidative Stress / Bilverdin / Nonsteroidal Anti-inflammatory Drug (NSAID) / 一酸化窒素合成酵素(iNOS) / グルタミン酸受容体 / プロティンキナーゼC / Peroxisome Proliferator-activated receptor-γ(PPARγ) / 一過性前脳虚血 / カイニン酸
Research Abstract

It is known that glial cells such as microglia and astrocytes are relatively resistance to stress of cell injury in comparison with neuronal cells. Under severe injury in the brain, glial cells induced inducible nitric oxide (NO) synthase (iNOS) and produced massive NO amount, and then surrounding neuronal cells underwent to apoptotic cell death. It is also known that biliverdin, which is produced by heme oxygenase (HO), is a potent endogenous anti-oxidant . Therefore, we focused the heme oxygenase and studied HO function in this research project. In the models of hippocampal injury such as 1) transient forebrain ischemia, 2) intracerebroventricular microinjection of kainate and 3) intrahippocampal microinjection of lipopolysaccharide and interferon-γ, the protein level of inducible HO(HO-1) was significantly increased in the hippocampus, but the lever of constitutive HO (HO-2) did not changed. One day after transient ischemia, HO-1 was markedly induced in hippocampal CA1 neurons, but subsequently, HO-1 level was decreased and neuronal loss was occurred. On the other hand, microglia and astrocytes continuously induced HO-1 and then did not die in these hippocampal injury models. Thus, the cells continuously expressing HO-1 may resistance to die.
Next we searched drugs which markedly induce HO-1, The agonists of metabotropic glutamate receptor induced HO-1 mediated by activation of protein kinase C. Surprisingly, nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, and ligands of transcription factor PPARγsuch as 15-d PGJィイD22ィエD2 inhibited induction of iNOS and NO production, but markedly induced HO-1 in cultured glial cells. These results suggest that several NSAIDs and PRARγligands are useful for cell protection on the brain injury.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Yoshihisa Kitamura: "In vitro and in vivo induction of heme oxygenase-1 in rat glial cells : Possible involvement of nitric oxide production from inducible nitric oxide synthase"Glia. 22・2. 138-148 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura: "Induction of inducible nitric oxide synthase and hemo oxygenase-1 in rat glial cells"Life Sciences. 62・17/18. 1717-1721 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka: "Kainic acid induction of heme oxygenase in vivo and in vitro"Neuroscience. 85・4. 1223-1233 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka: "Induction of heme oxygenese-1 and major histocompatibility complex antigens in transient forebrain ischemia"Journal of Cerebral Blood Flow and Metabolism. 18・8. 824-832 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura: "Activators of peroxisome proliferator-activated receptor-γ(PPARγ) inhibit inducible NO synthase expression but increase heme oxygenase-1 expression in rat glial cells"Neuroscience Letters. 262・2. 129-132 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka: "Expression of heme oxygenase-1 mediated by non-NMDA and metabotropic receptors in glial cells : Possible involvement of reactive oxygene species production and protein kinase C activation"Neuropharmacology. 38・6. 825-834 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura, et al.: "In vitro and in vivo induction of heme oxygenase-1 in rat glial cells : possible involvement of nitric oxide production from inducible nitric oxide synthase."GLIA. 22(2). 138-148 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura, et al.: "Induction of inducible nitric oxide synthase and heme oxygenase-1 in rat glial cells"Life Science. 62(17/18). 1717-1721 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka, et al.: "Kainic acid induction of heme oxygenase in vivo and in vitro."Neuroscience. 85(4). 1223-1233 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka, et al.: "Induction of heme oxygenase-1 and major histocompatibility complex antigens in transient forebrain ischemia"J.Cereb. Blood Flow Metab.. 85(4). 824-832 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura, et al.: "Activators of peroxisome proliferator-activated receptor-(PPARγ) inhibit inducible NO synthase expression but increase heme oxygenase-1 expression in rat glial cells."Neurosci.Latt.. 262(2). 129-132 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuji Matsuoka, et al.: "Expression of heme oxygenase-1 mediated by non-NMDA and metabotropic receptors in glial cells-Possible involvement of reactive oxygene species production and protein kinase C activation."Neuropharmacology. 38(6). 825-834 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihisa Kitamura: "Acivators of peroxisome proliferator-activated receptor-γ(PPARγ)inhibit inducible NO synthase expression but increase heme oxygense-1 expression in rat glial cells."Neuroscience Letters. 262・2. 129-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuji Matsuoka: "Expression of heme oxygense-1 mediated by non-NMDA and metabotropic receptors in glial cells:Possible involvement of reactive oxygene species production and protein kinase C activation."Neuropharmacology. 38・6. 825-834 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshihisa Kitamura: "In vitro and in vivo induction of heme oxygenase-1 in rat glial cells : Possible involvement of nitric oxide production from inducible nitric oxide synthase." Glia. 22・2. 138-148 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshihisa Kitamura: "Induction of inducible nitric synthase and heme oxygenase-1 in rat glial cells." Life Sciences. 62・17/18. 1717-1721 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasuji Matsuoka: "Kainic acid induction of heme oxygenase in vivo and vitro." Neuroscience. 85・4. 1223-1233 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasuji Matsuoka: "Induction of heme oxygenese-1 and major histocompatibility complex antigens in transient forebrain ischemia." Journal of Cerebral Blood Flow and Metabolism. 18・8. 824-832 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松岡 康治: "一過性前脳虚血におけるヘムオキシゲナーゼの誘導:虚血性神経細胞死" 山嶋哲盛編:サイメッド・パブリケーションズ社, 5頁(総頁数:190) (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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