Propofol attenuates hydrogenperoxide-induced apoptosis in human umbilical vein endothelial cells via multiple signaling pathways

BACKGROUND: Propofol has been reported to protect vascular endothelial cells against oxidative stress. In this study we investigated its effect on hydrogen peroxide (H(2)O(2))-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and examined the possible signaling pathways. METHODS: HUVECs were pretreated with propofol (1, 5, 25, and 50 µM) for 30 min and then co-incubated with 0.4 mM H(2)O(2) for 4 h. Cell viability was assessed using a Cell Counting Kit-8. Cell apoptosis was analyzed using flow cytometry with annexin V/propidium iodide staining, and evaluated by quantifying caspase-3, Bax, and Bcl-2 expression levels. The expression levels of p38 mitogen activated protein kinase (MAPK), phosphorylated (p)-p38 MAPK, cJun-N-terminal kinases (JNK), phosphorylated (p)-JNK, Akt and phosphorylated Akt [(p)-Akt] (Ser473) were measured by western blotting. RESULTS: H(2)O(2) treatment induced the activation of caspase-3, downregulated Bcl-2 expression, and up-regulated Bax expression, all of which were dose-dependently attenuated by propofol pretreatment. Furthermore, propofol significantly ameliorated H(2)O(2)-induced phosphorylation of p38 MAPK, JNK, and Akt in HUVECs. CONCLUSIONS: Propofol can protect HUVECs against H(2)O(2)-induced apoptosis via a mechanism that may involve p38 MAPK, JNK, and Akt signaling pathways.