Calcium/calmodulin-dependent kinase II facilitated GluR6 subunit serine phosphorylation through GluR6-PSD95-CaMKII signaling module assembly in cerebral ischemia injury.
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 Ca(2+) 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.
Xu
Jing
J
Laboratory of Biological Cancer Therapy, Xuzhou Medical College 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002 PR China.
Liu
Zhi-An
ZA
Pei
Dong-Sheng
DS
Xu
Tie-Jun
TJ
D000704:Analysis of Variance; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D047468:Immunoprecipitation / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D000097806:GluK2 Kainate Receptor; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009543:Nifedipine; D047428:Protein Kinase Inhibitors; D018092:Kainic Acid Receptors; D012694:Serine; D013449:Sulfonamides; D000097806:GluK2 Kainate Receptor; C501449:Dlg4 protein, rat; C072105:KN 93; D000096926:Benzenesulfonamides