Propofol protects against hydrogen peroxide-induced apoptosis in cardiac H9c2 cells is associated with the NF-κB activation and PUMA expression.

BACKGROUND AND AIMS Treatment with propofol has been found to attenuate oxidative stress injury in rat cardiac cells through the inhibition of programmed cell death. However, the underlying mechanism of this beneficial effect is not clear. Previous studies showed NF-κB (NF-κB) could be activated after oxidative stress in cardiac cells, and p53 up-regulated modulator of apoptosis (PUMA) is a direct target of NF-κB and mediates oxidative stress -induced apoptosis. Here, we report that propofol protects cardiac H9c2 cells from hydrogen peroxide (H2O2)-induced apoptosis by preventing the activation of NF-κB and PUMA upregulation. MATERIALS AND METHODS We first determined NF-κB activity, PUMA expression, proliferation and apoptosis after hydrogen peroxide treatment of the H9c2 cell line using electrophoretic mobility shift assay (EMSA), western blot assay, MTT and annexin V/PI assay. We, then, examined the effect of inhibition of NF-κB activity on the PUMA expression and hydrogen peroxide (H2O2)-induced apoptosis.We next examined the effect of inhibition of PUMA on hydrogen peroxide (H2O2)-induced apoptosis. In the end, we examined the effect of propofol pretreatment on NF-κB activity, PUMA expression and hydrogen peroxide (H2O2)-induced apoptosis. RESULTS We show that H2O2 treatment led to increases in NF-κB activity, PUMA protein levels in cardiac H9c2 cells. The induction of PUMA was mediated by the p65 component of NF-κB. The apoptotic effect of PUMA induction by H2O2 was in an NF-κB-dependent manner. We, further, demonstrate that pretreatment with propofol significantly decreased H2O2-induced apoptosis. Furthermore, propofol inhibits H2O2 induced NF-κB activity and subsequent PUMA expression. CONCLUSIONS our results reveal a new mechanism by which propofol inhibits H2O2-induced injury in cardiac H9c2 cells via decreasing NF-κB activation and PUMA expression. This inhibition improves cell survival, which provides a novel explanation for the pleiotropic effects of propofol that benefit the cardiac cells.

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