Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons

doi:10.1016/S0006-8993(99)02364-1

	Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons
	Jiang, Q ; Gu, ZL ; Zhang, GY ; Jing, GZ
刊名	BRAIN RESEARCH
	2000-02-28
卷号	857 期号:1-2 页码:71-77
关键词	ERK glutamate excitotoxicity apoptotic-like death cultured cortical neuron rat
ISSN号	0006-8993
DOI	10.1016/S0006-8993(99)02364-1
文献子类	Article
英文摘要	Glutamate-induced excitotoxicity, with certain characteristics of apoptosis, has been implicated in a variety of neuronal degenerative disorders. In some physiological cases, extracellular signal-regulated kinases (ERK1/2) are activated by stimulation of glutamate receptors. In the present study, the activation (diphosphorylation) and role of ERK1/2 in glutamate-induced apoptotic-like death in cultured cortical neurons were investigated. Protein levels and activation (diphosphorylation) levels of ERK1/2 were examined by Western immunoblot, probed with anti-ERK1/2 and anti-active (diphosphorylated) ERK1/2 antibodies, respectively. Apoptotic-like death was determined by DAPI staining. Before a remarkable increase of apoptotic-like cell death was observed at 9-18 h after 15 min exposure to 50 mu M glutamate, diphosphorylation levels of ERK1/2 were rapidly increased, peaked at 5-15 min of the exposure, and reverted to sham control level 3 h after the exposure, while the protein levels of ERK1/2 were unaffected. The glutamate concentration effective for inducing apoptotic-like cell death was correlated with that for inducing ERK1/2 diphosphorylation. Both ERK1/2 diphosphorylation and the apoptotic-like cell death were largely prevented by MK-801, a specific NMDA receptor (a subtype receptor of glutamate) antagonist, or the elimination of extracellular Ca2+ with EGTA. PD98059, a specific inhibitor of ERK1/2 kinase, completely inhibited ERK1/2 diphosphorylation and partially inhibited the apoptotic-like cell death. These results suggest that largely via NMDA receptor-mediated influx of extracellular Ca2+, ERK1/2 were rapidly and transiently activated and were involved in glutamate-induced apoptotic-like death in cultured rat cortical neurons. (C) 2000 Elsevier Science B.V. All rights reserved.
WOS关键词	ACTIVATED PROTEIN-KINASE ; MAP KINASE ; TYROSINE PHOSPHORYLATION ; HIPPOCAMPAL-NEURONS ; DEPENDENT MECHANISM ; CALCIUM INFLUX ; STIMULATION ; PATHWAY ; GROWTH ; BRAIN
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000085657200008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274642]
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.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Jiangsu 221002, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Q,Gu, ZL,Zhang, GY,et al. Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons[J]. BRAIN RESEARCH,2000,857(1-2):71-77.
APA	Jiang, Q,Gu, ZL,Zhang, GY,&Jing, GZ.(2000).Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons.BRAIN RESEARCH,857(1-2),71-77.
MLA	Jiang, Q,et al."Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons".BRAIN RESEARCH 857.1-2(2000):71-77.