title: NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through CaMKIIalpha in rat hippocampus during early global ischemia.
abstract: The phosphorylation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors subunit GluR1 at Ser831 has been implicated in the regulation of AMPA receptors channel. In this paper, Ser831 phosphorylation of GluR1 in rat hippocampus was investigated, which significantly increased during early global ischemia. To further illustrate the underlying mechanisms, calcium/calmodulin-dependent kinase IIalpha (CaMKIIalpha) inhibitor 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), CaM antagonist trifluoperazine (TFP), N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DEX), AMPA receptor antagonist 6,7-dinitro-quinoxaline-2,3-(1H,4H)-dione (DNQX) and L-type voltage-gated Ca2+ channel (L-VGCC) blocker nifedipine (NIF), were respectively administrated to the rats 20 min prior to ischemia. The results showed that KN62, TFP and DEX significantly attenuated Ser831 phosphorylation of GluR1, while DNQX and NIF had no obvious effects. Consequently, the studies suggest that early global ischemia induced Ser831 phosphorylation of GluR1 may be closely associated with CaMKIIalpha and the NMDA receptor, while the immediate Ser831 phosphorylation of GluR1 may have been involved in pathogenic events after early global ischemia.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Xin-Zhen
authors.initials: XZ
authors.lastname: Fu
authors.forename: Quan-Guang
authors.initials: QG
authors.lastname: Zhang
authors.forename: Fan-Jie
authors.initials: FJ
authors.lastname: Meng
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Zhang
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003720:Densitometry / Q000379:methods; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002121:Calcium Channel Blockers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009543:Nifedipine; D018091:Receptors, AMPA; D012694:Serine; D014268:Trifluoperazine; C063302:KN 62; C517675:Camk2a protein, rat