title: NMDA receptor/L-VGCC-dependent expression and AMPA/KA receptor-dependent activation of c-Jun induced by cerebral ischemia in rat hippocampus.
abstract: Over-activation of ionotropic glutamate receptors can cause an excessive influx of calcium ions into neurons, which subsequently triggers the degeneration and death of cells in a process known as excitotoxicity. Here, we examined the effects of modulating ionotropic glutamate receptors and L-type voltage-gated calcium channels (L-VGCC) on the expression and activation of c-Jun in hippocampus of SD rats after transient global ischemia. The total protein of c-Jun was altered by ischemia-reperfusion and reached its high levels at 3-6 h of reperfusion. However, the increased expression was prevented by pretreatment of ketamine (a non-competitive N-methyl-D-aspartate (NMDA) receptors antagonist) or nifedipine (a blocker of L-VGCC), but not by 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), an AMPA/KA receptor antagonist. On the other hand, c-Jun phosphorylation was significantly increased 3 h after reperfusion, which was inhibited by DNQX, but not ketamine or nifedipine. AP-1 binding activity reactions were also performed by electrophoretic mobility shift assay (EMSA), which detected similar results as those in Western blotting. Our results clearly showed that c-Jun expression is NMDA receptor/L-VGCC-dependent and c-Jun activation is AMPA/KA receptor-dependent, which expands our knowledge of the JNK-c-Jun signaling pathway in ischemic brain damage.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Quan-Guang
authors.initials: QG
authors.lastname: Zhang
authors.forename: Yong-Ling
authors.initials: YL
authors.lastname: Xu
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D016893:Carotid Stenosis / Q000150:complications; D004789:Enzyme Activation; D006624:Hippocampus / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015424:Reperfusion; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D048031:JNK Mitogen-Activated Protein Kinases; D007649:Ketamine; D009543:Nifedipine; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018808:Transcription Factor AP-1; C056723:FG 9041