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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-11-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
955
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia.
pubmed:affiliation
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't