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2000 Fiscal Year Final Research Report Summary

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
Keywordsbrain / glia / ischemia / apoptosis / stress protein / chaperon / caspase / nitric oxide
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.

  • Research Products

    (8 results)

All Other

All Publications (8 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)

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      「研究成果報告書概要(和文)」より
  • [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)

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      「研究成果報告書概要(和文)」より
  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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Published: 2002-03-26  

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