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

• Published in: Acta pharmacologica Sinica Vol. 25; no. 2; pp. 176 - 180
• Main Author: Fan-jieMENG JunGUO BoSONG Xue-boYAN Guang-yiZHANG
• Format: Journal Article
• Language: English
• Published: 2004
• Subjects: N-甲基-D-冬氨酸受体亚型2B; PSD-95; 动物实验; 脑组织; 脑缺血; 蛋白激酶; 钙调节素
• ISSN: 1671-4083; 1745-7254

AIM: To investigate the interactions among postsynaptic density 95 (PSD-95), Ca^2+-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. Immunoprecipitation 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-piperazine (KN-62, a selective inhibitor of CaMKⅡ) on these protein interactions were investigated. Coimmunoprecipitation 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 10min 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.