2001 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	森山芳則岡山大学, 薬学部, 教授 (10150658) 滝口正樹千葉大学, 医学部, 教授 (40179578)
キーワード	視交叉上核 / CaMキナーゼII / 概日リズム / 時計遺伝子 / マイクロアレイ / グルタミン酸 / 松果体 / メラトニン
研究概要	福永らは視神経刺激により誘発される視交叉上核でのシナプス伝達長期増強(LTP)の細胞内機序を調べた。LTPの発現は一酸化窒素合成酵素阻害剤とCaMキナーゼII(CaM KII)阻害剤によって完全に抑制された。メラトニンはCaM KII活性を抑制して,LTPを阻害した(論文投稿中)。in vivoにおいて光刺激によるPer 1の発現にはCaM KIIが関与していた。ルシフェラーゼ・レポーターを用いてPer1プロモーター活性に対する種々の活性型キナーゼの効果を検討した。MAPKとcAMPキナーゼによって1.5倍に、CaM KIIによって3倍に活性化された。CaMキナゼIVは効果を示さなかった。CaM KIIへの反応エレメントを決定した。反応エレメントに作用する既知の転写因子であるSP-1,C/EBPbetaは効果を示さなかった。今後は、CaM KII反応エレメントに結合する転写因子の同定と、概日リズムにおける生理的役割を明らかにする。滝口らは視交叉上核にて概日変動する遺伝子の検索を行うことを目的として、マウス視交叉上核mRNAに対するcDNAライブラリーの構築、マイクロアレイ解析の方法論を確立した。森山らはメラトニンの出力系の解析を行い、メラトニン分泌の抑制に関与するグルタミン酸作動系について解析した。マイクロベジクルにおけるグルタミン酸濃縮装置である小胞型グルタミン酸輸送体を同定した。また、メラトニン合成に中心的役割を果たす酵素N-acetylransferaseの活性調節に分子内S-S結合が関与する新しい制御系を見出した。

研究成果

(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Yonehara, T.: "Involvement of mitogen-activated protein kinase in cyclic adenosine 3',5'-monophosphate-induced hormone gene expression in rat pituitary GH_3 cells"Endocrinology. 142. 2811-2819 (2001)
[文献書誌] Yokota, S.-I.: "Involvement of calcium-calmodulin protein kinase but not of mitogen-activated protein kinase in light-induced phase delay and Per gene expression in the suprachiasmatic nucleus of hamster"J. Neurochem.. 77. 618-627 (2001)
[文献書誌] Kasahara, J.: "Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region"J. Biol. Chem.. 276. 24044-24050 (2001)
[文献書誌] Kawano, T.: "Neuroprotective effect of sodium orthovanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 1268-1280 (2001)
[文献書誌] Morioka, M.: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochem. Biophys. Res. Commun.. 286. 802-806 (2001)
[文献書誌] Kimura, T.: "CCAAT/enhancer-binding protein β is required for activation of genes for ornithine cycle enzymes by glucocorticoids and glucagon in primary-cultured hepatocytes"FEBS Lett.. 494. 105-111 (2001)
[文献書誌] Sugahara, K.: "Mice lacking CCAAT/enhancer-binding protein-α show hyperproliferation of alvelar type II cells and increased surfactant protein mRNAs"Cell Tissue Res.. 306. 57-63 (2001)
[文献書誌] Oyadomari, S.: "Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway"Proc. Natl. Acad. Sci. USA. 98. 10845-10850 (2001)
[文献書誌] Shimada, H.: "Facilitation of adenoviral wild-type p53-induced apopotic cell death by over expression of p33INGI in T.Tn human esophageal carcinoma cells"Oncogene. 21. 1208-1226 (2001)
[文献書誌] Hiwasa, T.: "Regulation of transformed state by calpastatin via PKCε in NIH3T3 mouse fibroblasts"Biochem. Biophys. Res. Commun.. 290. 510-517 (2002)
[文献書誌] Yamada, H.: "Ca^<2+>-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells"Diabetes. 50. 1012-1020 (2001)
[文献書誌] Nakatsuka, S.: "D-aspartate is stored in secretory granules and released through a Ca^<2+>-dependent pathway in a subset of rat pheochromocytome PC12 cells"J. Biol. Chem.. 276. 26589-26596 (2001)
[文献書誌] Hayashi, M.: "Differentiation-associated Na^+-dependent inorganic phosphate cotransporter(DNPI) is a vesicular glutamate transpoter in endocrine glutamatergic systems"J. Biol. Chem.. 276. 43400-43406 (2001)
[文献書誌] Hayashi, M.: "A homologue of N-ethylmaleimide-sensitive factor in teh malaria parasite plasmodium falciparum is export and localized in vesicular structures in the cytoplasm of infeted erythrocytes in the brefeldin A-sensitive pathway"J. Biol. Chem.. 276. 15249-15255 (2001)
[文献書誌] Sakata, K.: "Cloning of a lymphatic peptide/histidine transporter"Biochem. J.. 15. 53-60 (2001)
[文献書誌] 森山芳則: "グルタミン酸作動性パラ神経"ファルマシア. 37. 496-500 (2001)
[文献書誌] Yamada, H.: "Norepinephrine triggers Ca^<2+>-dependent exocytosis of 5-hyroxytryptamine from rat pinealocytes in culture"J. Neurochem.. (in press). (2002)
[文献書誌] Miyamoto, E.: "Involvement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. In : Neuroscientific Basis of Dementia (eds. : C.Tanaka, P.L.McGeer, Y.Ihara)"Birkhauser Verlag, Basel, Switzerland. 9 (2001)
[文献書誌] Fukunaga, K.: "Differential role of CaM kinases II and IV activities in neuronal plasticity and memory. In : Recent Research Developments in Neurochemistry."Research Signpost, Trivandrum, India(in press). (2002)

2001 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] Yonehara, T.: "Involvement of mitogen-activated protein kinase in cyclic adenosine 3',5'-monophosphate-induced hormone gene expression in rat pituitary GH_3 cells"Endocrinology. 142. 2811-2819 (2001)

[文献書誌] Yokota, S.-I.: "Involvement of calcium-calmodulin protein kinase but not of mitogen-activated protein kinase in light-induced phase delay and Per gene expression in the suprachiasmatic nucleus of hamster"J. Neurochem.. 77. 618-627 (2001)

[文献書誌] Kasahara, J.: "Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region"J. Biol. Chem.. 276. 24044-24050 (2001)

[文献書誌] Kawano, T.: "Neuroprotective effect of sodium orthovanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 1268-1280 (2001)

[文献書誌] Morioka, M.: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochem. Biophys. Res. Commun.. 286. 802-806 (2001)

[文献書誌] Kimura, T.: "CCAAT/enhancer-binding protein β is required for activation of genes for ornithine cycle enzymes by glucocorticoids and glucagon in primary-cultured hepatocytes"FEBS Lett.. 494. 105-111 (2001)

[文献書誌] Sugahara, K.: "Mice lacking CCAAT/enhancer-binding protein-α show hyperproliferation of alvelar type II cells and increased surfactant protein mRNAs"Cell Tissue Res.. 306. 57-63 (2001)

[文献書誌] Oyadomari, S.: "Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway"Proc. Natl. Acad. Sci. USA. 98. 10845-10850 (2001)

[文献書誌] Shimada, H.: "Facilitation of adenoviral wild-type p53-induced apopotic cell death by over expression of p33INGI in T.Tn human esophageal carcinoma cells"Oncogene. 21. 1208-1226 (2001)

[文献書誌] Hiwasa, T.: "Regulation of transformed state by calpastatin via PKCε in NIH3T3 mouse fibroblasts"Biochem. Biophys. Res. Commun.. 290. 510-517 (2002)

[文献書誌] Yamada, H.: "Ca^<2+>-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells"Diabetes. 50. 1012-1020 (2001)

[文献書誌] Nakatsuka, S.: "D-aspartate is stored in secretory granules and released through a Ca^<2+>-dependent pathway in a subset of rat pheochromocytome PC12 cells"J. Biol. Chem.. 276. 26589-26596 (2001)

[文献書誌] Hayashi, M.: "Differentiation-associated Na^+-dependent inorganic phosphate cotransporter(DNPI) is a vesicular glutamate transpoter in endocrine glutamatergic systems"J. Biol. Chem.. 276. 43400-43406 (2001)

[文献書誌] Hayashi, M.: "A homologue of N-ethylmaleimide-sensitive factor in teh malaria parasite plasmodium falciparum is export and localized in vesicular structures in the cytoplasm of infeted erythrocytes in the brefeldin A-sensitive pathway"J. Biol. Chem.. 276. 15249-15255 (2001)

[文献書誌] Sakata, K.: "Cloning of a lymphatic peptide/histidine transporter"Biochem. J.. 15. 53-60 (2001)

[文献書誌] 森山芳則: "グルタミン酸作動性パラ神経"ファルマシア. 37. 496-500 (2001)

[文献書誌] Yamada, H.: "Norepinephrine triggers Ca^<2+>-dependent exocytosis of 5-hyroxytryptamine from rat pinealocytes in culture"J. Neurochem.. (in press). (2002)

[文献書誌] Miyamoto, E.: "Involvement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. In : Neuroscientific Basis of Dementia (eds. : C.Tanaka, P.L.McGeer, Y.Ihara)"Birkhauser Verlag, Basel, Switzerland. 9 (2001)

[文献書誌] Fukunaga, K.: "Differential role of CaM kinases II and IV activities in neuronal plasticity and memory. In : Recent Research Developments in Neurochemistry."Research Signpost, Trivandrum, India(in press). (2002)

2001 年度実績報告書

福永浩司熊本大学, 医学部, 助教授 (90136721)