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. 2008 Feb 1;23(2):107–112. doi: 10.1007/s12264-007-0015-0

N-methyl-D-aspartate receptors mediate diphosphorylation of extracellular signal-regulated kinases through Src family tyrosine kinases and Ca2+/calmodulin-dependent protein kinase II in rat hippocampus after cerebral ischemia

脑缺血时NMDA受体通过Src激酶和Ca2+/钙调蛋白依赖性蛋白激酶II调控ERKs激活

Hui-Wen Wu 1, Hong-Fu Li 2, Jun Guo 3,✉
PMCID: PMC5550594  PMID: 17592533

Abstract

Objective

Extracellular signal-regulated kinases (ERKs) can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global cerebral ischemia.

Methods

Cerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot.

Results

Lethal-simulated ischemia significantly resulted in ERKs activation in N-methyl-D-aspartate (NMDA) receptor-dependent manner, accompanying with differential upregulation of Src kinase and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activities. With the inhibition of Src family tyrosine kinases or CaMKII by administration of PP2 or KN62, the phosphorylation of ERKs was impaired dramatically during post-ischemia recovery. However, ischemic challenge also repressed ERKs activity when Src kinase was excessively activated.

Conclusions

Src family tyrosine kinases and CaMKII might be involved in the activation of ERKs mediated by NMDA receptor in response to acute ischemic stimuli in vivo, but the intense activation of Src kinase resulted from ischemia may play a reverse role in the ERKs cascade.

Keywords: cerebral ischemia, extracellular signal-regulated kinases, NMDA receptors, Src family tyrosine kinases, CaMKII

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