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.
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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)
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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
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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)
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