Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia

doi:10.1016/S0006-8993(02)03376-0

	Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia
	Hou, XY ; Zhang, GY ; Yan, JZ ; Chen, M ; Liu, Y
刊名	BRAIN RESEARCH
	2002-11-15
卷号	955 期号:1-2 页码:123-132
关键词	brain ischemia PSD95 Fyn NMDA receptor L-type voltage-gated calcium channel hippocampus
ISSN号	0006-8993
DOI	10.1016/S0006-8993(02)03376-0
文献子类	Article
英文摘要	Recent studies have indicated that tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A) by Src family kinases (Src, Fyn, etc.) up-regulates NMDA receptors activity and postsynaptic density protein 95 kDa (PSD95) may mediate the regulation. To investigate whether the above processes are involved in brain ischemia-induced enhancement of NMDA receptors function, we examined the effects of transient (15 min) brain ischemia followed by reperfusion on interactions involving Fyn, NR2A and PSD95 in rat hippocampus by co-immunoprecipitation. Transient brain ischemia was induced by the method of four-vessel occlusion in Sprague-Dawley rats. Association between Fyn and NR2A increased immediately after brain ischemia and the increase was maintained for at least 24 h during followed reperfusion, up to about 1.7-1.8-fold relative to sham-groups. The 15-min reperfusion after brain ischemia induced enhanced co-immunoprecipitation of PSD95, Fyn and NR2A with one another. The associations of PSD95 with Fyn and NR2A increased at 0-24 h, 0-1 h of reperfusion, up to 6.9- and 2.1-fold relative to sham groups, respectively. Inhibiting activation of NMDA receptors or L-type voltage-gated calcium channels (L-VGCC) by ketamine or nifedipine attenuated the above increases of associations. These results suggest that stimulation of NMDA receptors and L-VGCC facilitates formation of a ternary complex: Fyn-PSD95-NR2A during transient brain ischemia followed by reperfusion, which may result in potentiation of NMDA receptor function and contribute to ischemic neuronal cell death. (C) 2002 Elsevier Science B.V. All rights reserved.
WOS关键词	D-ASPARTATE RECEPTOR ; POSTSYNAPTIC DENSITY FRACTION ; TYROSINE PHOSPHORYLATION ; SRC-FAMILY ; CEREBRAL-ISCHEMIA ; SUBUNIT 2B ; KINASE-C ; PROTEIN ; PSD-95 ; FYN
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000179424800014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274309]
专题	中国科学院上海药物研究所
通讯作者	Zhang, GY
作者单位	1.Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Hou, XY,Zhang, GY,Yan, JZ,et al. Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia[J]. BRAIN RESEARCH,2002,955(1-2):123-132.
APA	Hou, XY,Zhang, GY,Yan, JZ,Chen, M,&Liu, Y.(2002).Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia.BRAIN RESEARCH,955(1-2),123-132.
MLA	Hou, XY,et al."Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia".BRAIN RESEARCH 955.1-2(2002):123-132.