Activation (phosphorylation) and the possible mechanism of extracellular signal-regulated kinase 5 (ERK5) were evaluated after cerebral ischemia-reperfusion (I/R) in the hippocampus in a four-vessel occlusion model of Sprague-Dawley rats. Western blotting showed that ERK5 was strongly activated from 10 min to 1 day and peaked at 30 min of reperfusion after 15 min ischemia. Pretreatment with N-acetylcysteine, a free radical scavenger, effectively inhibited ERK5 activation in a dose-dependent manner. Consistently, ERK5 activation was significantly suppressed by genistein (protein-tyrosine kinase inhibitor), PP2 (specific inhibitor of Src family kinases), nifedipine (L-VGCC blocker) and dextromethorphan (NMDA receptor antagonist), but not 6,7-dinitroquinoxaline-2, 3(1H, 4H)-dione (AMPA receptor antagonist). These results suggested that ERK5 could be significantly activated by I/R, which might be mediated by NMDA receptor and L-VGCC through Src kinase pathway involving oxidative stress in rat hippocampus.
- Cerebral ischemia
- Extracellular signal-regulated kinase 5
- N-methyl-D-aspartate receptor
ASJC Scopus subject areas