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Mechanisms of cellular and intracellular functions in brain-immune qnetwork.

Research Project

Project/Area Number 10307055
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

NOMURA Yasuyuki  Hokkaido Univ., Grad.Sch.of Pharma.Sci., Professor, 大学院・薬学研究科, 教授 (00034041)

Co-Investigator(Kenkyū-buntansha) MURAYAMA Toshihiko  Chiba Univ., Professor, 薬学部, 教授 (90174317)
UEHARA Takashi  Hokkaido Univ., Associate Professor, 大学院・薬学研究科, 助教授 (00261321)
OKUMA Yasunobu  Hokkaido Univ., Associate Professor, 大学院・薬学研究科, 助教授 (20127939)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥37,200,000 (Direct Cost: ¥37,200,000)
Fiscal Year 2000: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥20,200,000 (Direct Cost: ¥20,200,000)
Keywordsbrain / glia / ischemia / apoptosis / stress protein / chaperon / caspase / nitric oxide / ニューロン / アストログリア / 一酸化窒素 / 一酸化窒素合成酵素 / カスパーゼ / DNA断片化 / HSP70
Research Abstract

We investigated the mechanisms of 1) ischemia-induced neuronal cell death and 2) acquisition of tolerance against ischemic stress in glial cells. Hypoxia, an ischemic stress, induced neuronal apoptosis via cytochrome c release from mitochondria and following caspase activation. On the other hand, this stress up-regulated some stress proteins such as a 70 kDa heat-shock protein (HSP70) and a 78 kDa glucose-regulated protein (GRP78). In addition, we found that HSP70 induction was sensitive to SB203580, suggesting that p38 MAP kinase was positively involved in this expression. We further attempted to identify a stress protein that was enhanced or induced by hypoxia or brain ischemia in glial cells. We isolated protein-disulfide isomerase (PDI) as a candidate protein and this protein certainly induced in glial cells of ischemic brain. Overexpression of PDI in vitro and in vivo resulted in attenuation of the loss of cell viability in neuroblastoma SK-N-MC cells and a reduction in the number of DNA-fragmented cells in the CA1 subfield of the hippocampus in brain ischemic rats, respectively. Thus, up-regulated PDI may play a critical role in resistance to ichemic damage.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Uehara,T. et al: "Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells."Brain Res.. 790. 284-292 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uehara,T. et al: "Caspase activation accompanying cytochrome C release from mitochondria is possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells."J.Neurochem.. 72(1). 196-205 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyazaki,H. et al: "Glial cell linederived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats."Neuroscinece. 89(3). 643-647 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uehara,T. et al: "Transient NF-κB activation stimulated by interleukin-1β may be party dependent on proteasome activity, but not phosphorylation and ubiquitination of IκBα molecule, in C6 glioma cells."J.Biol.Chem.. 274(22). 15875-15882 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito,A. et al: "Possible involvement of cytochrome c release and sequential activation of caspase-2 and -3 in ceramide-induced apoptosis in SK-N-MC cells."Biochem.Biophys.Acta.. 1452. 263-274 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,S. et al: "Up-regulation of protein disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death."J.Biol.Chem.. 275(14). 10388-10393 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 野村靖幸: "脳NO:グリア・ニューロン相関における死のメッセンジャー「心血管病態とNO」"金芳堂. 10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 野村靖幸: "脳機能解析法,in vivo解析:脳の細胞分子生物学-神経細胞のアポトーシス,「脳科学マニュアル」"北海道大学図書刊行会. 9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishiya, T.et al: "Involvement of nuclear factor-κB(NF-κB)signaling in the expression of inducible nitric oxide synthase(iNOS)gene in rat Co glioma cells."Biochem.Biophys.Res.Commun.. 275. 268-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka, S.et al: "Up-regulation of protein-disulfide isomerase in reseponse to hypoxia/brain ischemia and its protective effect against apoptotic cell death."J.Biol.Chem.. 275(14). 10388-10393 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyazaki, H.et al: "Glial cell line-derived neurotrophic factor modulates ischemia-induced tyrosine hydroxylase expression in rat hippocampus."Europ.J.Neurosci.. 12. 2032-2038 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito, A.et al: "Isolation of lch-1S(caspase-2S)-binding protein that partially inhibits caspase activity."FEBS Lett.. 470. 360-364 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tha, K.K.et al: "Changes in expressions of proinflammatory cytokines IL-1β,TNF-α and IL-6 in the brain of senescence accelerated mouse(SAM)P8."Brain Res.. 885. 25-31 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Moriya, R.et al: "Mechanism of nitric oxide-induced apoptosis in human neuroblastoma SH-SY5Y cells."FEBS Lett.. 484. 253-260 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Uehara, T., et al: "Caspase activation accompanying cytochrome C release from mitochondria is possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells"J. Neurochem.. 72(1). 196-205 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyazaki, H., et al: "Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats"Neuroscience. 89(3). 643-647 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uehara, T., et al: "Possible involvement of p38 MAP kinase in HSP70 expression induced by hypoxia in rat primary astrocytes"Brain Res.. 823. 226-230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uehara, T., et al: "Transient NF-κB activation stimulated by interleukin-Iβ may be party dependent on proteasome activity, but not phosphorylation and ubiquitination of IκBα molecule, in C6 glioma cells"J. Biol. Chem.. 274(22). 15875-15882 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito, A., et al: "Possible involvement of cytochrome c release and sequential activation of caspases in ceramide-induced apoptosis in SK-N-MC cells"Biochem. Biophys. Acta. 1452. 263-274 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuda, Y., et al: "Inhibition of hydrogen peroxide-induced apoptosis but not archidonic acid release in GH3 cell by EGF"Brain Res. 850. 197-206 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 野村 靖幸: "脳科学マニュアル"北大刊行会. 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nomura, Y., et al: "Innovative Animal Models of Central Nervous System Disease"The Humana Press (Massachusetts). 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murayam, T.et al: "Regulation of inducible NO synthase expression by endothelin in primary cultured glial cells." Life Sci.62・17/18. 1491-1495 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshinaga,N.et al: "Death by a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP^+) and protection by EGF in GH3 Cells." Brain Res.794. 137-142 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uehara,T.et al: "Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells." Brain Res.790. 284-292 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyakoshi,M.et al: "Regulation of cyclic GMP and cyclic AMP production by S-nitroso-cysteine in rat thymocytes." Europ.J.Pharmacol.359. 235-241 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Araya,R.et al: "Hypoxia induces apoptosis human neuroblastoma SK-N-NC cells caspase activation accompanying cytochrome C release from mitochondria." FEBS Lett.439. 168-172 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uehara,T.et al: "Caspase activation accompanying cytochrome C release from mitochondria possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells." J.Neurochem.72・1. 196-205 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 野村靖幸: "アストロサイトにおけるNO合成酵素の誘導と脳ニューロン死, 「脳機能の解明」(赤池紀扶 編)" 九州大学出版会, 10 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 野村靖幸: "脳NO:グリア・ニューロン相関における死のメッセンジャー, 「心血管病態とNO」(島田和幸ら 編)" 金芳堂, 10 (1998)

    • Related Report
      1998 Annual Research Report

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

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