Intracellular Ca(2+) homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis

BACKGROUND: Perioperative hypoxia may induce microglial inflammation and apoptosis, resulting in brain injury. The neuroprotective effect of propofol against hypoxia has been reported, but the underlying mechanisms are far from clear. In this study, we explored whether and how propofol could attenuate microglia BV2 cells from CoCl(2)-induced hypoxic injury. METHODS: Mouse microglia BV2 cells were pretreated with propofol, and then stimulated with CoCl(2). TNF-α level in the culture medium was measured by ELISA kit. Cell apoptosis and intracellular calcium concentration were measured by flow cytometry analysis. The effect of propofol on CoCl(2)-modulated expression of Ca(2+)/Calmodulin (CaM)-dependent protein kinase II (CAMKIIα), phosphorylated CAMKIIα (pCAMKIIα), STAT3, pSTAT3(Y705), pSTAT3(S727), ERK1/2, pERK1/2, pNFκB(p65), pro-caspase3, cleaved caspase 3, JAK1, pJAK1, JAK2, pJAK2 were detected by Western blot. RESULTS: In BV2 cell, CoCl(2) treatment time-dependently increased TNF-α release and induced apoptosis, which were alleviated by propofol. CoCl(2) (500μmol/L, 8h) treatment increased intracellular Ca(2+) level, and caused the phosphorylation of CAMKIIα, ERK1/2 and NFκB (p65), as well as the activation of caspase 3. More importantly, these effects could be modulated by 25μmol/L propofol via maintaining intracellular Ca(2+) homeostasis and via up-regulating the phosphorylation of JAK1 and STAT3 at Tyr705. CONCLUSION: Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca(2+) homeostasis and the activation of JAK1/STAT3 pathway.