Calcium/calmodulin-dependent protein kinase II (CaMKII), through NMDA receptors and L-Voltage-gated channels, modulates the serine phosphorylation of GluR6 during cerebral ischemia and early reperfusion period in rat hippocampus.
Recent studies have shown that GluR6 is involved in the modulation of neuronal cell death. It has been shown that PKA can phosphorylate recombinant GluR6 homomeric receptors and that this phosphorylation of GluR6 was suggested to underlie an enhancement of whole-cell current responses. Here, we try to find out whether brain ischemia and reperfusion could induce any change in the serine phosphorylation of GluR6. Our results showed that the serine phosphorylation of GluR6 increased in hippocampus during brain ischemia and early reperfusion period. Then, we used several drugs to investigate the mechanism of modulating the serine phosphorylation of GluR6. KT5720, a specific cell-permeable inhibitor of protein kinase A (PKA), had no effect on the increase in serine phosphorylation of GluR6 induced by brain ischemia or reperfusion. On the other hand, KN-62, a selective inhibitor of rat brain Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), diminished the increase in serine phosphorylation of GluR6. Moreover, our results showed that either MK801 (a NMDA receptor antagonist) or Nifedipine (a L-type Ca2+ channel (L-VGCC) blocker) decreased the increase in serine phosphorylation. In conclusion, our results suggest that CaMKII, activated through NMDA receptors and L-VGCCs, mediated the serine phosphorylation of GluR6 during brain ischemia and early reperfusion period.
Hao
Zhi-Bin
ZB
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
Pei
Dong-Sheng
DS
Guan
Qiu-Hua
QH
Zhang
Guang-Yi
GY
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015424:Reperfusion; D000097806:GluK2 Kainate Receptor
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020746:Calcium Channels, L-Type; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D009543:Nifedipine; D010768:Phosphoserine; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D000097806:GluK2 Kainate Receptor; C063302:KN 62