Signal transducer and activator of transcription-3 activation is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated Ca2+ channel during cerebral ischemia in rat hippocampus.
It has been proved that signal transducer and activator of transcription-3 (STAT3) is expressed and activated following cerebral ischemia/reperfusion in cortex and striatum. Here we investigated the changes in tyrosine phosphorylation and DNA-binding activity of STAT3 in hippocampus in a four-vessel occlusion model of Sprague-Dawley rats. Phospho-STAT3 (in cytoplasm) was enhanced from 5 min and reached its peak level at 10 min of ischemia. While in nucleus, phospho-STAT3 increased from 10 min and then peaked at 30 min of ischemia. Concomitantly, DNA-binding activity of STAT3 demonstrated a similar rule in nucleus extracts. The increased tyrosine phosphorylation and DNA-binding activity of STAT3 in nucleus were blocked by ketamine, an N-methyl-D-aspartate receptor antagonist, or by nifedipine, a L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist. These results illustrated that the ionotropic glutamate receptor and L-VGCC are important in mediating STAT3 activation during severe cerebral ischemia.
Li
Hongchun
H
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, PR China.
Zhang
Quanguang
Q
Zhang
Guangyi
G
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D024202:Electrophoretic Mobility Shift Assay; D006624:Hippocampus / Q000378:metabolism*; D015151:Immunoblotting; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis*; D014443:Tyrosine / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004268:DNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014443:Tyrosine; D007649:Ketamine; D009543:Nifedipine