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 Ca2+ 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. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.