N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death

doi:10.1016/S0006-8993(00)03003-1

	N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death
	Jiang, Q ; Gu, ZL ; Zhang, GY ; Jing, GZ
刊名	BRAIN RESEARCH
	2000-12-29
卷号	887 期号:2 页码:285-292
关键词	extracellular signal-regulated kinase excitotoxicity glutamate receptor protein kinase protein phosphatase cortical neuron
ISSN号	0006-8993
DOI	10.1016/S0006-8993(00)03003-1
文献子类	Article
英文摘要	Extracellular signal-regulated kinases (ERK1/ERK2) have been shown transiently activated and involved in excitotoxicity. We searched for upstream molecules responsible for the regulation of glutamate-induced ERK1/ERK2 activation and ERK1/ERK2-mediated apototic-like death in cultured rat cortical neurons. ERK1/ERK2 activation (monitored by anti-active ERK1/ERK2 antibody) was almost completely prevented by blockage of NMDA receptor (NMDA-R) or elimination of extracellular Ca2+, but not any other glutamate receptor or L-type voltage-gated Ca2+ channel. It was prevented largely by inhibition of protein kinase C (PKC), protein-tyrosine kinases (PTK), respectively, but mildly by that of CaM kinase II. Combined inhibition of CaM kinase IJ (but not PTK) and PKC had an additive effect. Reversion of ERK1/ERK2? activation was largely prevented by inhibition of protein phosphatase (PP) 1 or protein tyrosine phosphatase (PTP). Combined inhibition of PP 1 and PTP had no additive effect. Glutamate-induced apoptotic-like death (determined by DAPI staining) was largely prevented by inhibition of NMDA-R, PKC, CaM kinase II, PTK and MEK1/MEK2 (ERK1/ERK2 kinase). respectively. Combined inhibition of CaM kinase II (but not PKC or PTK) and MEK1/MEK2 had an additive effect. Glutamate-induced apoptotic-like death was promoted by inhibition of PP1 and PTP, respectively. The above results suggested that in glutamate-induced cortical neurotoxicity ERK1/ERK2? activation be mainly mediated by NMDA-R. Subsequently, a pathway dependent on both PKC and PTK was mainly involved, which was also mainly responsible for ERK1/ERK2-mediated apoptotic-like death, and a CaM kinase II-dependent pathway was relatively mildly involved. Reversion of ERK1/ERK2 activation was mainly mediated by a pathway dependent on both PPI and PTP, which might be involved in the restrain of glutamate-induced neurotoxicity. (C) 2000 Elsevier Science B.V. All rights reserved.
WOS关键词	CEREBELLAR GRANULE NEURONS ; APOPTOTIC-LIKE DEATH ; NITRIC-OXIDE ; MAP KINASE ; TYROSINE PHOSPHORYLATION ; PRIMARY CULTURE ; DENTATE GYRUS ; CYCLIC-AMP ; CELL-DEATH ; RAT-BRAIN
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000166116900006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274545]
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 221001, 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	Jiang, Q,Gu, ZL,Zhang, GY,et al. N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death[J]. BRAIN RESEARCH,2000,887(2):285-292.
APA	Jiang, Q,Gu, ZL,Zhang, GY,&Jing, GZ.(2000).N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death.BRAIN RESEARCH,887(2),285-292.
MLA	Jiang, Q,et al."N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death".BRAIN RESEARCH 887.2(2000):285-292.