• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Molecular Cell Biological Study on Neuronal Apoptosis in Cerebellar Graneul Cells

Research Project

Project/Area Number 10480216
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

HATANAKA Hiroshi  Inst. Prot. Res., Osaka Univ., Professor, 蛋白質研究所, 教授 (60208519)

Co-Investigator(Kenkyū-buntansha) IKEUCHI Toshihiko  Inst. Prot. Res., Osaka Univ., Associate Professor, 蛋白質研究所, 助教授 (20093362)
Project Period (FY) 1998 – 1999
KeywordsApoptosis / PI3-kinase / SNF-1 / Neurotrophin / High potassium / Cereberum / Phosphorylation / Low potassium
Research Abstract

We analyzed the mechanism underlying cell death using cultured rat cerebellar granule and cerebral cortical neurons, because of their abundance and homogeneity. Cerebellar granule neurons maintained in medium containing 26 mM potassium or in medium (5 mM potassium) with 50 ng/ml BDNF undergo an apoptoic cell death when exposed to 10 μ M LY294002, an inhibitor of PI3-kinase. To investigate the intracellular signaling mechanism of LY294002-induced apoptosis, the activities of Akt and c-Jun N-terminal kinase (JNK) were measured in cells in HKィイD1+ィエD1 (26 mM potassium) or LKィイD1+ィエD1 (5 mM potassium) medium containing BDNF, with or without 10 μ M LY294002. Akt activity decreased following the addition of 10 μ M LY294002. In addition, we found that LY294002 increased the JNK activity, which is known to mediate some types of cell death in PNS neurons. We also observed elevated expression of c-Jun by LY294002 in HKィイD1+ィエD1 +BDNF. These findings demonstrated that apoptosis induced by inhibition of PI3-kinase activity involves suppression of the Akt activity and elevation of the JNK activity in cerebellar granule neurons. Our results suggested that the PI3-kinase-Akt pathway suppresses the activation of JNK and c-Jun expression, and as a result prevents the neuronal cell death in cerebellar granule neurons.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 荒木敏行ら: "Role of phosphatase activity of Shp-2 in BDNF signaling in cultured cerebral cortical neurons."J.Neurochem.,. 74,. 659-668 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 稲村直子ら: "The role of p53 in DNA strand break-induced apoptosis in organotypic slice cultures from the mouse cerebellum."J.Neurosci.Res.,. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 下家浩二ら: "Inhibition of phosphatidylinositol 3-kinase activity elevates c-Jun-terminal kinase activity in apoptosis of cultured cerebellar granule neurons."Dev.Brain Res.,. 112,. 245-253 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石川保幸ら: "Generation of reactive oxygen species,release of L-glutamate and activation of caspase are required for the high oxygen-induced apoptpsis of embrvonic hippocampal neurons in culture."Brain Res.,. 824,. 71-80 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田雅司ら: "BDNF stimulates interaction of Shp2 with PI3-K and Grb2 in cultured cerebral cortical neurons."J.Neuochem.,. 73,. 41-49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤託実ら: "Regulation of reactive oxygen species by nerve growth factor but not by Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death."J.Biochem.,. 125,. 952-959 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 畠中寛、: "化学同人"「化学の未来へ」脳細胞の神秘にせまる-アポトーシスは脳をときあかす鍵-. 238(3-17) (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田雅司、畠中寛: "羊土社"「新アポトーシス実験法-基本操作と最先端の解析方-」培養中枢神経細胞を用いたアポトーシスの解析. 307(149-157) (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Araki, M. Yamada, H. Ohnishi, S. Sano, T. Uetsuki and H. Hatanaka: "Role of phosphatase activity of Shp-2 in BDNF signaling in cultured cerebral cortical neurons."J. Neurochem. 74. 659-668 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Inamura, T. Araki, Y. Enokido, C. Nishio, S. Aizawa, and H. Hatanaka: "The role of p53 in DNA strand break-induced apoptosis in organotypic slice cultures from the mouse cerebellum."J. Neurosci. Res. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Shimoke, S. Yamagishi, M. Yamada, T. Ikeuchi and H. Hatanaka: "Inhibition of phosphatidylinositol 3-kinase activity elevates c-Jun N-terminal kinase activity in apoptosis of cultured cerebellar granule neurons."Dev. Brain Res. 112. 245-253 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Ishikawa, T. Satoh, Y. Enokido, C. Nishio, T. Ikeuchi and H. Hatanaka: "Generation of reactive oxygen species, release of L-glutamate and activation of caspase are required for the high oxygen-induced apoptosis of embryonic hippocampal neurons in culture"Brain Res. 824. 71-80 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Yamada, H. Ohnishi, S. Sano, A. Nakatani, T. Ikeuchi and H. Hatanaka: "BDNF stimulates interaction of Shp2 with P13-K and Grb2 in cultured cerebral cortical neurons"J. Neuochem. 73. 41-49 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Satoh, T. Yamagata, Y. Ishikawa, M. Yamada, Y. Uchiyama and H. Hatanaka: "Regulation of reactive oxygen species by nerve growth factor but not by Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death."J. Biochem. 125. 952-959 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Satoh, T. Numakawa, Y. Abiru, T. Yamagata, Y. Ishikawa, Y. Enokido and H. Hatanaka: "Production of reactive oxygen species and release of L-glutamate during superoxide anion-induced apoptosis of cerebellar granule neurons."J. Neurochem. 70. 316-324 (1998)

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

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi