2015 Volume 26 Issue 2 Pages 233-237
The signal transducers and activators of transcription (STAT) were found to be essential for the regulation of apoptosis and cell death initiated by a pro-survival signaling cascade. In focal cerebral ischemia, STAT3 tyrosine 705 phosphorylation has been demonstrated in neurons and activation of STAT3 is correlated with neuronal survival. However, the precise role of STAT3 serine phosphorylation remains unclear. In this study, we examined the phosphorylation status of ser727-STAT3 in the hippocampal CA1 region by using a rat transient global ischemia model. Western blot analysis showed that ser727-STAT3 phosphorylation was induced in hippocampal CA1 neurons after ischemia. Ser727-STAT3 phosphorylation transiently increased in the early stage of reperfusion after lethal ischemia, in contrast, it gradually increased in a time-dependent manner and peaked at 2 day after nonlethal ischemia. In the preconditioned brains, it also increased in the early stage of reperfusion, however, decrease of its levels delayed compared to the nonconditioned brains. Furthermore, inhibition of STAT3 phosphorylation abolished preconditioning-induced neuroprotection. Our results suggest that activation of ser727-STAT3 after nonlethal ischemia is closely associated with acquisition of ischemic tolerance. Although further investigation is necessary to clarify the exact role of STAT3 serine phosphorylation in neuroprotection, STAT3 can be an important target for stroke therapy.
