Competitive binding of postsynaptic density 95 and Ca2+-calmodulin dependent protein kinase II to N-methyl-D-aspartate receptor subunit 2B in rat brain

作     者：Fan-jie MENG , Jun GUO, Bo SONG, Xue-bo YAN, Guang-yi ZHANG2 Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China 

作者机构：Research Center of Biochemistry and Molecular Biology Xuzhou Medical College Xuzhou 221002 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2004年第25卷第2期

页      面：50-54页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：Project supported by the National Natural Science Foundation of China. No 39470186 30070182 

主　　题：N-methyl-D-aspartate receptors Ca2+-calmodulin dependent protein kinase brain ischemia 

摘      要：AIM: To investigate the interactions among postsynaptic density 95 (PSD-95), Ca2+-calmodulin dependent protein kinase IIα (CaMKIIα), and N-methyl-D-aspartate receptor subunit 2B (NR2B) during ischemia and reperfusion in hippocampus of rats. METHODS: Brain ischemia was induced by four-vessel occlusion procedure in rats. Immu- noprecipitation and immunoblotting were performed to study the interactions and phosphorylation of proteins. The association-dissociation of PSD-95 and CaMKIIα to and from N-methyl-D-aspartate (NMDA) receptor induced by ischemia and reperfusion and the effects of 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-pip- erazine (KN-62, a selective inhibitor of CaMKII) on these protein interactions were investigated. Coimmuno- precipitation and immunoblotting were performed for the studies of interactions among proteins. RESULTS: The alternations of the binding level of PSD-95 and CaMKIIα to NR2B during ischemia and reperfusion demonstrated the negative correlation to each other. Pre-administration of KN62 through both cerebral ventricles inhibited the 10 min ischemia-induced increase of the binding of PSD-95 to NR2B and, on the contrary, promoted the binding of CaMKIIα to NR2B. CONCLUSION: PSD-95 competes with CaMKII to bind to NR2B during ischemia and reperfusion in rat hippocampus.