The Mechanism of Ischemic Preconditioning Up-Regulation the Expression of Tissue Kallikrein Protects Neurons from Cerebral Ischemia/Reperfusion Injury

Abstract

Ischemic stroke is an important clinical problem with few effective treatments. Many studies have shown that exogenous tissue kallikrein (TK) can protect neurons against hypoxia/reoxygenation injury. In the present study, we explored the possible molecular mechanisms underlying the regulation and function of endogenous TK. Western blot, chromatin immunoprecipitation (ChIP) and real-time PCR (RT-PCR) revealed that cerebral ischemic preconditioning (IP) upregulated the expression of endogenous TK by regulating the acetylation of histone H3. Cresyl violet staining was used to assess the neuroprotective role of endogenous TK on rat hippocampal CA1 neurons against cerebral ischemia/reperfusion (I/R) injury. Western blot results showed that IP activated the expression of p-Raf, p-MEK1/2 and p-ERK1/2 by Western blot. Moreover, Western blotfurther determined that endogenous TK upregulated the expression of p-Bad, depressed the release of cytochrome c and Bax from mitochondria to the cytosol and inhibited caspase-3 activation. In conclusion, endogenous TK can play a neuroprotective role and its upregulation induced by IP treatment can activate the phosphorylation of Raf, MEK1/2 and p-ERK1/2, depress the release of cytochrome c and Bax from mitochondria to the cytosol and inhibit caspase-3 activation.