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.
- Author:
Hui-Wen WU
1
;
Hong-Fu LI
;
Jun GUO
Author Information
- Publication Type:Journal Article
- MeSH: Analysis of Variance; Animals; Brain Ischemia; enzymology; pathology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; metabolism; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; metabolism; Gene Expression Regulation; physiology; Hippocampus; cytology; enzymology; Male; Neurons; enzymology; pathology; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; metabolism; Signal Transduction; physiology; Statistics, Nonparametric; src-Family Kinases; metabolism
- From:Neuroscience Bulletin 2007;23(2):107-112
- CountryChina
- Language:English
-
Abstract:
OBJECTIVEExtracellular 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.
METHODSCerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot.
RESULTSLethal-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.
CONCLUSIONSrc 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.
