2000 Fiscal Year Annual Research Report

海馬シナプス可塑性におけるカルモデュリンキナーゼIIの役割

Research Project

Project/Area Number	11170244
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)	笠原二郎熊本大学, 医学部, 助手 (10295131) 山本秀幸熊本大学, 医学部, 講師 (60191433) 宮本英七熊本大学, 医学部, 教授 (50109659)
Keywords	long-term potemtiation / CaMキナーゼII / CaMキナーゼIV / MAPキナーゼ / プロテインホスファターゼ / CREB / 海馬 / 学習
Research Abstract	カルモデュリン(CaM)キナーゼIIは海馬シナプス伝達長期増強(LTP)の発現に関与している。LTPに伴うスバインでのAMPA受容体(GluR1)の発現はCaMキナーゼII依存性である。本研究ではシナプスにおけるCaMキナーゼIIの標的分子を明らかにして,神経活動依存性のシナプス再構成の分子素過程を追究寸ゐ。海馬LTPの誘発刺激で活性化されたCaMキナーゼIIはプロテインホスファターゼ2A(PP2A)の調節サブユニットB'を燐酸化して,活性を抑制すること見出した。B'は主に,海馬CA1錐体細胞の樹上突起に発現していた。PP2A活性の抑制はCaMキナーゼIIの自己燐酸化反応や他のプロテインキナーゼの活性化反応を介して,LTPの発現と維持に関与していると考えられる。海馬LTPにおける維持・固定のプロセスには転写調節因子,CREBの燐酸化反応が関与している。海馬でのCREB燐酸化酵素であるMAPキナーゼとCaMキナーゼIVの海馬LTPにおける活性化反応の時間経過について明らかにした。海馬LTP誘発刺激に伴って、MAPキナーゼとCaMキナーゼIVは一過性に活性化された。これに対してCREBの燐酸化反応は持続的であった。阻害剤を用いた実験から、LTP誘発直後のCREB燐酸化反応にはCaMキナーゼIVが持続的なCREB燐酸化反応にはMAPキナーゼとCaMキナーゼIVの両者が関与することが解った。今後は種々の学習モデルの学習獲得過程におけるCaMキナーゼII,IVとMAPキナーゼの活性化反応の時間的,空間的解析を行う予定である。

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 MlN6 cells."Endocrinology. 141. 2350-2360 (2000)
[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocarcinoma 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

海馬シナプス可塑性におけるカルモデュリンキナーゼIIの役割

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 MlN6 cells."Endocrinology. 141. 2350-2360 (2000)

[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocarcinoma 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)