2001 Fiscal Year Annual Research Report

時計遺伝子産物のリン酸化に関わる分子素過程の解明

Research Project

Project/Area Number	11233205
Research Institution	Kumamoto University
Principal Investigator	福永浩司熊本大学, 医学部, 助教授 (90136721)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Morioka, M.: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochem. Biophys. Res. Commun.. 286. 802-806 (2001)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Hiwasa, T.: "Regulation of transformed state by calpastatin via PKCε in NIH3T3 mouse fibroblasts"Biochem. Biophys. Res. Commun.. 290. 510-517 (2002)
[Publications] Yamada, H.: "Ca^<2+>-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells"Diabetes. 50. 1012-1020 (2001)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Sakata, K.: "Cloning of a lymphatic peptide/histidine transporter"Biochem. J.. 15. 53-60 (2001)
[Publications] 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)
[Publications] Yamada, H.: "Norepinephrine triggers Ca^<2+>-dependent exocytosis of 5-hyroxytryptamine from rat pinealocytes in culture"J. Neurochem.. (in press). (2002)
[Publications] 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)
[Publications] 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 Fiscal Year Annual Research Report

時計遺伝子産物のリン酸化に関わる分子素過程の解明

Principal Investigator

福永 浩司 熊本大学, 医学部, 助教授 (90136721)

Research Products

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

福永浩司熊本大学, 医学部, 助教授 (90136721)