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1995 Fiscal Year Final Research Report Summary

Molecular Pharmacological studies on the neuron/glia network

Research Project

Project/Area Number 06454595
Research Category

Grant-in-Aid for General Scientific Research (B)

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

Principal Investigator

NOMURA Yasuyuki  Hokkaido Univ., Fac.of Pharma.Sci.Professor, 薬学部, 教授 (00034041)

Project Period (FY) 1994 – 1995
KeywordsNitric oxide synthase(NOS) / Inducible NOS(iNOS) / Endotoxin / Interferon-gamma(IFN-gamma) / Herbimycin A / NF-kB / JAK2 / STAT1alpha
Research Abstract

Nitric oxide (NO) is believed to be involved in neurotoxicity after various neuronal stresses and in synaptic plasticity in the cerebellum and thehippocampus in the central nervous system. In the brain, a constitutively expressed NO synthase (cNOS) is expressed in specific neuronal populations, whereit can act as mentioned above. On the other hand, another type of NOS,inducible NOS (iNOS) , is induced by treatment with bacterial endotoxin (lipopolysaccharide, LPS) and/or cytokines in brainglial cells. However, the signal transduction system responsible for induction of iNOS is poorly understood. We examined the induction mechanism of iNOS stimulated by LPS plus interferon-gamma(IFN-gamma) in C6 glioma cells. LPS or IFN-gamma alone could not induce iNOS,but combination of LPS plus IFN-gamma markedly induced iNOS in C6 glioma sells. We found that pretreatment with herbimycin A,apotent selective tyrosine kinase inhibitor, suppressed the induction of NOS by LPS plus IFN-gamma. LPS activated NF-kBand this effect was also sensitive to herbimycin A.On the other hand, IFN-gammastimulated tyrosine-phosphorylation ofJAK2 and STAT1alpha and translocation of STAT1alphato nuclei. These activation by IFN-gamma was also inhibited by herbimycin A.Taken together, these findings suggestthat dual signal transduction pathwaysare required to induce NOS in C6 glioma cells and a tyrosine-kinase is involved in the NF-kB activation.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Itano, Y: "1-Methy-4-phenyl pryidinium (MPPP^+)-induced cell death in PC12 cells : Inhibitory effects of several drugs." Neurochem. Int.25. 419-424 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itano, Y: "Biphasic effects of MPPP^+), a possible parkinsonism inducer, on dopamine content and tyrosine hydroxylase mRNA expression in PC12 cells." Neurochem. Int.26. 165-171 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura Y.: "Inhibition by pentamidine on constitutive nitric oxide synthase in the brain : as a celmodulin antagonist." Europ. J. Pharmacol.289. 299-304 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara T.: "Wortmannin inhibits insulin-induced ras and mitogen-acitivated protein kinase activation related to adipocyre differentiation in 3T3-Lifibroblasis." Biochem. Biophys. Res. Commun.210. 574-580 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiya T.: "Herblmycin A suppresses NF-κB activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells." FEBS Lett.371. 333-336 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura Y.: "Inducible type of nitric oxide synthase (i-NOS) in rat glial cells." Nitric Oxide-Roles in Neuronal Communication amd Neurotoxicity. 41-51 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村靖幸: "「脳機能の解明」 脳の老化 神経細胞死と記憶障害" 創風社, 8 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村靖幸: "「最新医学からのアプローチ(13)NO」グリアでのNO産生とニューロン死." メジカルレビュー社, 13 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura, Y.: "Induction of pentamidine on constitutive nitric oxide synthase in the brain : as a calmodulin antagonist" Europ.J.Pharmacology. 289. 299-304 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara, T.: "Wortmannin inhibits insulin-induced Ras and mitogen-activated protein kinase activation related to adipocyte differentiation in 3T3-L1 fibroblasts" Biochem.Biophys.Res.Commun.210. 574-580 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiya, T.: "Herbimycin A suppresses NF-kB activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells" FEBS Lett.371. 333-336 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitamura, Y.: "Inducible type of nitric oxide synthase(i-NOS)in rat glial cells" Nitric Oxide-Roles in Neuronal Communications and Neurotoxicity. 144-156 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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