Over-activation of ionotropic glutamate receptors can cause an excessive influx of calcium ions into neurons, which subsequently triggers the degeneration and death of cells in a process known as excitotoxicity. Here, we examined the effects of modulating ionotropic glutamate receptors and L-type voltage-gated calcium channels (L-VGCC) on the expression and activation of c-Jun in hippocampus of SD rats after transient global ischemia. The total protein of c-Jun was altered by ischemia-reperfusion and reached its high levels at 3-6 h of reperfusion. However, the increased expression was prevented by pretreatment of ketamine (a non-competitive N-methyl-d-aspartate (NMDA) receptors antagonist) or nifedipine (a blocker of L-VGCC), but not by 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), an AMPA/KA receptor antagonist. On the other hand, c-Jun phosphorylation was significantly increased 3 h after reperfusion, which was inhibited by DNQX, but not ketamine or nifedipine. AP-1 binding activity reactions were also performed by electrophoretic mobility shift assay (EMSA), which detected similar results as those in Western blotting. Our results clearly showed that c-Jun expression is NMDA receptor/L-VGCC-dependent and c-Jun activation is AMPA/KA receptor-dependent, which expands our knowledge of the JNK-c-Jun signaling pathway in ischemic brain damage.
- AMPA/KA receptor
- Cerebral ischemia
- L-Type voltage-gated Ca channel
- NMDA receptor
ASJC Scopus subject areas