| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4326307 | Brain Research | 2010 | 7 Pages |
Although recent results suggest that GluR6 serine phosphorylation plays a prominent role in brain ischemia/reperfusion-mediated neuronal injury, little is known about the precise mechanisms regulating GluR6 receptor phosphorylation. Our present study shows that the assembly of the GluR6–PSD95–CaMKII signaling module induced by brain ischemia facilitates the serine phosphorylation of GluR6 and further induces the activation of c-Jun NH2-terminal kinase JNK. More important, a selective CaMKII inhibitor KN-93 suppressed the increase of the GluR6–PSD95–CaMKII signaling module assembly and GluR6 serine phosphorylation as well as JNK activation. Such effects were similar to be observed by NMDA receptor antagonist MK801 and L-type Ca2+ channel (L-VGCC) blocker Nifedipine. These results demonstrate that NMDA receptors and L-VGCCs depended-CaMKII functionally modulated the phosphorylation of GluR6 via the assembly of GluR6–PSD95–CaMKII signaling module in cerebral ischemia injury.
Research Highlights►The definite existence and alteration of CaMKII–GluR6–PSD95 signaling module and involved in GluR6 serine phosphorylation during reperfusion. ►KN-93, MK-801 and Nifedipine suppress the CaMKII–GluR6–PSD95 signaling module assembly and GluR6 serine phosphorylation. ►KN-93, MK-801 and Nifedipine inhibit the JNK3 activation. ►KN-93, MK-801 and Nifedipine decrease neural injury after cerebral ischemia/reperfusion.
