1996 Fiscal Year Annual Research Report

小脳顆粒細胞アポトーシスの細胞内シグナルと酸素ラジカルの役割

Research Project

Project/Area Number	08780743
Research Institution	Osaka University
Principal Investigator	榎戸靖大阪大学, 蛋白質研究所, 助手 (90263326)
Keywords	癌抑制遺伝子 / DNA傷害 / プログラム細胞死 / アポトーシス / 小脳顆粒細胞 / 神経栄養因子 / ニューロトロフィン / チロシンキナーゼ
Research Abstract	小脳顆粒細胞は、中枢神経系におけるニューロン死の分子メカニズムを蛋白質ならびに遺伝子レベルで解析する上で極めて有効な実験材料である。昨年度より我々はこの系を用い、(1)ニューロトロフィンおよびそのレセプターを介した生存維持機構の細胞内シグナル伝達系ならびに(2)酸素ラジカルと脱分極刺激除去による中枢ニューロン死のメカニズムについて解析を行ってきた。本年度はまず第一に、幼若な小脳顆粒細胞に対する脳由来神経栄養因子(BDNF)およびNT-3による生存維持効果について、それぞれのレセプターであるTrkBおよびTrkCを介した細胞内シグナル伝達機構について解析を行った。その結果、それぞれのニューロトロフィンによる生存維持効果の差は、レセプターの発現量およびその下流に存在するリン酸化蛋白質の活性化の違いによることを明らかにした(Nonomura,et al.,Dev.Brain Res.,1996)。第二に、脱分極刺激除去による小脳顆粒細胞のアポトーシスでは、細胞周期関連遺伝子の一つであるサイクリンAの特異的な発現低下を伴う(Oka,et al.,Dev.Brain Res.,1996)と同時に、BDNFによる生存維持効果はP13キナーゼの活性化を介したものであることを示した(Shimoke,et al.,Dev.Brain Res.,reviced)。第三に、様々な酸素ストレスおよびDNA障害による中枢ニューロン死メカニズムの解析のため、癌抑制遺伝子p53遺伝子欠損マウス由来の小脳ニューロンを用い、酸素ラジカルによるニューロン死がグルタミン酸毒性やDNA鎖切断を介してアポトーシスを誘導することを明らかにした(Enokido,et al.,Neurosci.Lett.,1996;Enokido,et al.,Eur.J.Neurosci.,1996;Enokido,et al.,J.Neurochem.,reviced;Satoh,et al.,投稿準備中)。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Y.Enokido: "p53 involves cytosine arabinoside-induced apoptosis in cnltnred cerebellar granule neurons." Neuroscience Letters. 203. 1-4 (1996)
[Publications] T.Satoh: "Free radical-independent proteotion by nerve growth factor and the bc1-2 gene product of PC12 cells from hydrogen peroxide-induced apoptosis." The Journal of Biochemistry. 120. 540-546 (1996)
[Publications] T.Satoh: "Suruival factor-insensitive generation of reactive oxygen species induced by serum deprivation in neuronal cells." Brain Research. 733. 9-14 (1996)
[Publications] T.Kubo: "Oxygene-induced apoptosis in PC12 cells with special reference to the role of bc1-2" Brain Research. 733. 175-183 (1996)
[Publications] Y.Enokido: "Involvement of p53 in DNA strand break-induced apoptosis in postmitotic CNS neurons." The European Journal of Neuroscience. 8. 1812-1821 (1996)
[Publications] T.Nonomura: "Signaling pathways and suruiual effects of BDNF and NT-3 on cultured cerebellar granule cells." Developmental Brain Research. 97. 42-50 (1996)
[Publications] T.Oka: "Expression of cyclin A decreases during neuronal apoptosis in cultured rat cerebellar granule neurons." Developmental Brain Research. 97. 96-106 (1996)
[Publications] T.Kubo: "Apoptosis in cerebellar granule neurons." Advances in Neurological Sciences. 40. 197-205 (1996)
[Publications] H.Aoshima: "Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12h cells." Biochimica Biophysica Acta. (1997)
[Publications] Y.Enokido: "The loss of the xeroderma pigmentosum group A (XPA) geneenhances apoptosis of cultured cerebellar neurons induced by UV but not by low-k^+-medium" The Journal of Neurochemistry. (1997)
[Publications] T.Satoh: "Oxygen toxicity induce apoptosis in neuronal cells." Cellular and Molewlar Neurobiology. (1997)
[Publications] Y.Enokido: "The role of p53 in postmitotic CNS neurons" Journal of Braim Research. (1997)
[Publications] Y.Enokido: "Neurodegenerative Diseases" G.Fiskum, 482 (1996)

1996 Fiscal Year Annual Research Report

小脳顆粒細胞アポトーシスの細胞内シグナルと酸素ラジカルの役割

Principal Investigator

榎戸 靖 大阪大学, 蛋白質研究所, 助手 (90263326)

Research Products

[Publications] Y.Enokido: "p53 involves cytosine arabinoside-induced apoptosis in cnltnred cerebellar granule neurons." Neuroscience Letters. 203. 1-4 (1996)

[Publications] T.Satoh: "Free radical-independent proteotion by nerve growth factor and the bc1-2 gene product of PC12 cells from hydrogen peroxide-induced apoptosis." The Journal of Biochemistry. 120. 540-546 (1996)

[Publications] T.Satoh: "Suruival factor-insensitive generation of reactive oxygen species induced by serum deprivation in neuronal cells." Brain Research. 733. 9-14 (1996)

[Publications] T.Kubo: "Oxygene-induced apoptosis in PC12 cells with special reference to the role of bc1-2" Brain Research. 733. 175-183 (1996)

[Publications] Y.Enokido: "Involvement of p53 in DNA strand break-induced apoptosis in postmitotic CNS neurons." The European Journal of Neuroscience. 8. 1812-1821 (1996)

[Publications] T.Nonomura: "Signaling pathways and suruiual effects of BDNF and NT-3 on cultured cerebellar granule cells." Developmental Brain Research. 97. 42-50 (1996)

[Publications] T.Oka: "Expression of cyclin A decreases during neuronal apoptosis in cultured rat cerebellar granule neurons." Developmental Brain Research. 97. 96-106 (1996)

[Publications] T.Kubo: "Apoptosis in cerebellar granule neurons." Advances in Neurological Sciences. 40. 197-205 (1996)

[Publications] H.Aoshima: "Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12h cells." Biochimica Biophysica Acta. (1997)

[Publications] Y.Enokido: "The loss of the xeroderma pigmentosum group A (XPA) geneenhances apoptosis of cultured cerebellar neurons induced by UV but not by low-k^+-medium" The Journal of Neurochemistry. (1997)

[Publications] T.Satoh: "Oxygen toxicity induce apoptosis in neuronal cells." Cellular and Molewlar Neurobiology. (1997)

[Publications] Y.Enokido: "The role of p53 in postmitotic CNS neurons" Journal of Braim Research. (1997)

[Publications] Y.Enokido: "Neurodegenerative Diseases" G.Fiskum, 482 (1996)

榎戸靖大阪大学, 蛋白質研究所, 助手 (90263326)