Calcium/calmodulin-dependent kinase II facilitated GluR6 subunit serine phosphorylation through GluR6-PSD95-CaMKII signaling module assembly in cerebral ischemia injury.

Abstract

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.

• Authors: Jing Xu, Zhi-An Liu, Dong-Sheng Pei, Tie-Jun Xu
• Journal: Brain research (Brain Res) Vol. 1366 Pg. 197-203 (Dec 17 2010) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 20888327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Benzylamines
• Disks Large Homolog 4 Protein
• Dlg4 protein, rat
• Excitatory Amino Acid Antagonists
• Gluk2 kainate receptor
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Protein Kinase Inhibitors
• Receptors, Kainic Acid
• Sulfonamides
• KN 93
• Serine
• Dizocilpine Maleate
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Nifedipine

Topics

• Analysis of Variance
• Animals
• Benzylamines (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Disease Models, Animal
• Disks Large Homolog 4 Protein
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Immunoprecipitation (methods)
• In Situ Nick-End Labeling (methods)
• Injections, Intraventricular (methods)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Ischemic Attack, Transient (metabolism, pathology, physiopathology, therapy)
• Male
• Membrane Proteins (metabolism)
• Nifedipine (pharmacology, therapeutic use)
• Phosphorylation (drug effects, physiology)
• Protein Kinase Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Kainic Acid (metabolism)
• Serine (metabolism)
• Signal Transduction (physiology)
• Sulfonamides (pharmacology)