2000 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)	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)
Keywords	視交叉上核 / 概日リズム / CaMキナーゼII / CaMキナーゼIV / MAPキナーゼ / long-term potentiation / 時計遺伝子 / CREB
Research Abstract	本研究では24時間概日リズムの中枢である視交叉上核(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。ハムスターのSCNにおいて光刺激により、CaMキナーゼIIが活性化されることを証明した。行動リズムにおける光依存性同調に対してCaMキナーゼの阻害剤、KN93が抑制すること、MAPキナーゼの阻害剤であるPD98059は抑制しないことを示した。光同調機構にはSCNにおけるCREBのリン酸化反応とそれに続くc-Fosの発現が関与するという報告がある。また、CREBをリン酸化するキナーゼとしてはCaMキナーゼIIとCaMキナーゼIVが考えられる。これらのCaMキナーゼの活性型を認識する抗体を作製した。視交叉上核への入力線維、視神経を高頻度刺激すると視交叉上核での興奮性シナプス後電位の長期増強(LTP)が観察される。これは光依存性同調刺激に類似した反応である。このLTPに伴ってCaMキナーゼIVが核内で活性化されることを確認した。CaMキナーゼIIも同様に活性化されるが、その場所は主に、細胞質と樹状突起であった。以上の結果により、光依存性同調刺激にはCaMキナーゼが関与すること、視交叉上核における光刺激によるCREBのリン酸化反応にはCaMキナーゼIVが主に関わっていることが明らかとなった。今後はCREBのリン酸化反応から概日リズムの位相変化に至る細胞内シグナル伝達を明らかにする。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] K.Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J.Neurochem.. 74. 807-817 (2000)
[Publications] J.Kasahara: "Activation of Ca^<2+>/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons."J.Neurosci.Res.. 59. 594-600 (2000)
[Publications] K.Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5, 6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biochem.Pharmacol.. 60. 693-699 (2000)
[Publications] H.Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol.Reprod.. 62. 1486-1494 (2000)
[Publications] Y.Takeuchi: "Identification of the isoforms of Ca^<2+>/calmodulin-dependent protein kinase II in rat astrocytes and their subcellular localization."J.Neurochem.. 74. 2557-2567 (2000)
[Publications] H.Tabuchi: "Regulation of insulin secretion by overexpression of Ca^<2+>/calmodulin-dependent protein kinase II in insulinoma MIN6 cells."Endocrinology. 141. 2350-2360 (2000)
[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocar-cinoma cell line HEC-1B."Biol.Reprod.. 63. 933-941 (2000)
[Publications] T.Moriya: "Close linkage between calcium/calmodulin kinase II α/β and NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning."Eur.J.Neurosci.. 12. 3307-3314 (2000)
[Publications] Q.Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethy-lammonium-induced long-term potentiation."Biochem.Biophys.Res.Commun.. 267. 208-212 (2000)
[Publications] I.Munir: "Signaling pathways affecting cyclooxygenase 2 expression in endometrial epithelial cells."Recent Res.Devel.Endocrinol.. 1. 261-272 (2000)
[Publications] K.Fukunaga: "A working model of CaM kinase II activity in hippocampal long-term potentiation and memory."Neurosci.Res.. 38. 3-17 (2000)
[Publications] 福永浩司: "海馬における神経活動依存性シナプス伝達効率の調節."蛋白質核酸酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)
[Publications] S.-I.Yokota: "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.. (in press). (2001)
[Publications] T.Yonehara: "Involvement of mitogen-activated protein kinase in cAMP-induced hormone gene expression in rat pituitary GH3 cells."Endocrinology. (in press). (2001)
[Publications] E.Miyamoto: "Involvement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. Neuroscientific Basis of Dementia (eds.: C. Tanaka, P.L. McGeer, Y. Ihara)"Birkhauser Verlag, Basel, Switzerland. 9 (2001)

2000 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] K.Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J.Neurochem.. 74. 807-817 (2000)

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

[Publications] H.Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol.Reprod.. 62. 1486-1494 (2000)

[Publications] Y.Takeuchi: "Identification of the isoforms of Ca^<2+>/calmodulin-dependent protein kinase II in rat astrocytes and their subcellular localization."J.Neurochem.. 74. 2557-2567 (2000)

[Publications] H.Tabuchi: "Regulation of insulin secretion by overexpression of Ca^<2+>/calmodulin-dependent protein kinase II in insulinoma MIN6 cells."Endocrinology. 141. 2350-2360 (2000)

[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocar-cinoma cell line HEC-1B."Biol.Reprod.. 63. 933-941 (2000)

[Publications] T.Moriya: "Close linkage between calcium/calmodulin kinase II α/β and NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning."Eur.J.Neurosci.. 12. 3307-3314 (2000)

[Publications] Q.Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethy-lammonium-induced long-term potentiation."Biochem.Biophys.Res.Commun.. 267. 208-212 (2000)

[Publications] I.Munir: "Signaling pathways affecting cyclooxygenase 2 expression in endometrial epithelial cells."Recent Res.Devel.Endocrinol.. 1. 261-272 (2000)

[Publications] K.Fukunaga: "A working model of CaM kinase II activity in hippocampal long-term potentiation and memory."Neurosci.Res.. 38. 3-17 (2000)

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

[Publications] S.-I.Yokota: "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.. (in press). (2001)

[Publications] T.Yonehara: "Involvement of mitogen-activated protein kinase in cAMP-induced hormone gene expression in rat pituitary GH3 cells."Endocrinology. (in press). (2001)

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

福永浩司熊本大学, 医学部, 助教授 (90136721)