Propofol attenuates high glucose-induced superoxide anion accumulation in human umbilical vein endothelial cells.

Abstract

Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction, and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol attenuated high glucose-induced endothelial apoptosis, dysfunction, and inflammation via inhibiting reactive oxygen species (ROS) accumulation. However, the mechanisms by which propofol reduces high glucose-induced endothelial ROS accumulation are still obscure. In this study, we examined how propofol attenuates high glucose-induced endothelial ROS accumulation. Compared with 5 mm glucose treatment, 15 mm glucose upregulated the expression of pin-1, phosphatase A2 (PP2A), p66shc and mitochondrial p66shc expression, increased p66shc -Ser36 phosphorylation, and O2·- accumulation. More importantly, although propofol had no effect on 15 mm glucose-induced p66shc -Ser36 phosphorylation and pin-1 expression, propofol could downregulated PP2A expression and p66shc expression in whole-cell and mitochondrion, resulting in the reduction of O2·- accumulation. Moreover, we demonstrated that the antioxidative effect of propofol was similar to that of calyculin A, an inhibitor of PP2A. In contrast, FTY720, an activator of PP2A, antagonized the effect of propofol. Our data indicated that the antioxidative effect of propofol was achieved by downregulating PP2A expression, resulting in the inhibition of p66shc -Ser36 dephosphorylation and mitochondrial p66shc expression.