Activation of STAT3 induced by cerebral ischemia in rat hippocampus and its possible mechanisms.
It has been demonstrated that signal transducer and activator of transcription-3 (STAT3) is activated after cerebral ischemia/reperfusion (I/R) in cortex and striatum. In this study, we investigated whether STAT3 was rapidly activated in hippocampus by cerebral ischemia without reperfusion in four-vessel occlusion (4-VO) model of Sprague-Dawley (SD) rats. The results showed that tyrosine phosphorylation and DNA binding activity of STAT3 was rapidly increased by ischemia. The p-STAT3 level in cytoplasm increased 5 min after occlusion and reached a peak at 10 min following ischemia (1.7 folds vs sham) by means of immunoblotting (IB). P-STAT3 in nucleus was gradually enhanced with its peak activity occurring at 30 min of ischemia (2.3 folds vs sham). Electrophoretic mobility shift assay (EMSA) with STAT3 probe demonstrated that DNA binding activity of STAT3 in nuclear extracts increased from 5 min and peaked at 30 min of ischemia (3.2 folds vs sham). These changes were prevented by genistein (a protein tyrosine kinase inhibitor) and antioxidant N-acetyl-L-cysteine (NAC), but promoted by sodium orthovanadate (a protein phosphatase inhibitor), which were administered to the SD rats 20 min before ischemia. These results indicate that the activation of STAT3 following cerebral ischemia may be modulated by PTK/PTP, and that this pathway may be of benefit to the adaptation of the hippocampal neurons to oxidative stress.
Li
Hong-Chun
HC
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002.
Zhang
Guang-Yi
GY
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases