1999 年度実績報告書

時計遺伝子産物のリン酸化に関わる分子素過程の解明

研究課題

研究課題/領域番号	11233205
研究種目	特定領域研究(B)
研究機関	熊本大学
研究代表者	福永浩司熊本大学, 医学部, 助教授 (90136721)
研究分担者	宮本英七熊本大学, 医学部, 教授 (50109659) 滝口正樹千葉大学, 医学部, 教授 (40179578)
キーワード	視交差上核 / CaMキナーゼII / メラトニン / 概日リズム / 時計遺伝子 / long-term potentiation / MAPキナーゼ / CaMキナーゼIV
研究概要	本研究では視交差上核(SCN)における光依存性および非依存性の同調機構におけるCaMキナーゼ,MAPキナーゼの役割について明らかにする。最初に光同調機構と共通点の多い海馬の長期増強(LTP)におけるメラトニンの効果について検討した。メラトニンは培養海馬神経細胞において細胞質に存在するCaMキナーゼII活性には影響せず,核内に発現するCaMキナーゼIVを選択的に阻害した。一方,光非依存性同調因子であるセロトニン,ニューロンペプチドYは共に,CaMキナーゼII活性を有意に抑制した。さらに,海馬CA1領域において高濃度のメラトニンはLTPの発現を阻害した。今後は,SCNにおけるLTPの発現機構とLTP発現に対する光非依存性同調因子の効果を調べる。また,培養SCN神経細胞を用いてグルタミン酸受容体刺激に伴う細胞内燐酸化反応について解析する予定である。リセット機構のシグナル伝達の解析にはSCNの初代培養系が有益であるが,異なるポピュレーションの細胞が混在しているため,生化学的解析が不可能である。培養線維芽細胞,肝細胞では血清刺激によって時計関連遺伝子の概日リズムが誘発されることが知られている。CaMキナーゼIIを恒常的に発現させた腫瘍性線維芽細胞株を樹立した。今後は,血清刺激によるCaMキナーゼII,MAPキナーゼの活性化反応,および時計遺伝子関連蛋白質の燐酸化反応を解析することによって概日リズム発進機構とリセット機構のシグナル伝達系を解析する。

研究成果

(17件)

すべてその他

すべて文献書誌 (17件)

[文献書誌] M. Ohmitsu: "Phosphorylation of myristoylated alanine-rich protein kinase C substrate by mitogen-activated protein kinase in cultured rat hippocampal neurons following stimulation of glutamate receptors."J. Biol. Chem.. 274. 408-417 (1999)
[文献書誌] K. Matsumoto: "Cloning from insulinoma cells of synapsin I associated with insulin secretory granules."J. Biol. Chem.. 274. 2053-2059 (1999)
[文献書誌] N. Masuko: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90: A possible regulatory role in molecular clustering at synaptic sites."J. Biol. Chem.. 274. 5782-5790 (1999)
[文献書誌] J. Kasahara: "Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca^<2+>/calmodulin-dependent protein kinase in cultured rat hippocampal neurons."J. Biol. Chem.. 274. 9061-9067 (1999)
[文献書誌] H. Kuwahara: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-Methyl-D-aspartate receptor."J. Biol. Chem.. 274. 32204-32214 (1999)
[文献書誌] J. Liu: "Differential roles of Ca^<2+>/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation."J. Neurosci.. 19. 8292-8299 (1999)
[文献書誌] M. Morioka: "Activities of calcineurin and phosphatase 2A in the hippocampus after transient forebrain ischemia."Brain Res.. 828. 135-144 (1999)
[文献書誌] H. Kanasaki: "Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells."Biol. of Reprod.. 61. 319-325 (1999)
[文献書誌] I. Munir: "Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B."J. Reprod. Fertil.. 117. 49-59 (199)
[文献書誌] Q. Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethylammonium-induced long-term potentiation."Biochem. Biophys. Res. Commun.. 267. 208-212 (1999)
[文献書誌] K. Fukunaga: "Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory."Jpn. J. Pharmacol.. 79. 7-15 (1999)
[文献書誌] 福永浩司: "海馬における神経活動依存性シナプスの伝達効率の調節"蛋白質核酸酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)
[文献書誌] J. Kasahara: "Activation of Ca^<2+>/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons."J. Neurosci. Res.. 59. 594-600 (2000)
[文献書誌] K. Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J. Neurochem.. (in press). (2000)
[文献書誌] K. Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by DY-9760e, a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biolchem. Pharmacol.. (in press). (2000)
[文献書誌] H. Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol. of Reprod.. (in press). (2000)
[文献書誌] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章神経情報の統合,5.脳可塑性"共立出版. 7 (1999)

1999 年度 実績報告書

時計遺伝子産物のリン酸化に関わる分子素過程の解明

研究代表者

福永 浩司 熊本大学, 医学部, 助教授 (90136721)

研究成果

[文献書誌] M. Ohmitsu: "Phosphorylation of myristoylated alanine-rich protein kinase C substrate by mitogen-activated protein kinase in cultured rat hippocampal neurons following stimulation of glutamate receptors."J. Biol. Chem.. 274. 408-417 (1999)

[文献書誌] K. Matsumoto: "Cloning from insulinoma cells of synapsin I associated with insulin secretory granules."J. Biol. Chem.. 274. 2053-2059 (1999)

[文献書誌] N. Masuko: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90: A possible regulatory role in molecular clustering at synaptic sites."J. Biol. Chem.. 274. 5782-5790 (1999)

[文献書誌] J. Kasahara: "Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca^<2+>/calmodulin-dependent protein kinase in cultured rat hippocampal neurons."J. Biol. Chem.. 274. 9061-9067 (1999)

[文献書誌] H. Kuwahara: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-Methyl-D-aspartate receptor."J. Biol. Chem.. 274. 32204-32214 (1999)

[文献書誌] J. Liu: "Differential roles of Ca^<2+>/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation."J. Neurosci.. 19. 8292-8299 (1999)

[文献書誌] M. Morioka: "Activities of calcineurin and phosphatase 2A in the hippocampus after transient forebrain ischemia."Brain Res.. 828. 135-144 (1999)

[文献書誌] H. Kanasaki: "Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells."Biol. of Reprod.. 61. 319-325 (1999)

[文献書誌] I. Munir: "Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B."J. Reprod. Fertil.. 117. 49-59 (199)

[文献書誌] Q. Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethylammonium-induced long-term potentiation."Biochem. Biophys. Res. Commun.. 267. 208-212 (1999)

[文献書誌] K. Fukunaga: "Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory."Jpn. J. Pharmacol.. 79. 7-15 (1999)

[文献書誌] 福永浩司: "海馬における神経活動依存性シナプスの伝達効率の調節"蛋白質核酸酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)

[文献書誌] J. Kasahara: "Activation of Ca^<2+>/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons."J. Neurosci. Res.. 59. 594-600 (2000)

[文献書誌] K. Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J. Neurochem.. (in press). (2000)

[文献書誌] K. Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by DY-9760e, a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biolchem. Pharmacol.. (in press). (2000)

[文献書誌] H. Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol. of Reprod.. (in press). (2000)

[文献書誌] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章 神経情報の統合,5.脳可塑性"共立出版. 7 (1999)

1999 年度実績報告書

福永浩司熊本大学, 医学部, 助教授 (90136721)

[文献書誌] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章神経情報の統合,5.脳可塑性"共立出版. 7 (1999)