Propofol inhibits LPS-induced apoptosis in lung epithelial cell line, BEAS-2B

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Xiang Lv, Xuhui Zhou, Jia Yan, Jue Jiang, Hong Jiang
Lipopolysaccharide (LPS) plays an important role in lung endothelial apoptosis which is crucial for lung fibrogenesis in ARDS progression. Reactive oxygen species (ROS) has been reported to be involved in LPS-induced lung epithelial cell apoptosis. Propofol is a commonly used intravenous anesthetic agent in clinic and it could attenuate LPS-induced epithelial cells oxidation and apoptosis. However, the mechanisms are still obscure. In this study, we examined whether and how propofol attenuates LPS-induced oxidation and apoptosis in BEAS-2B cells. Compared with control group, LPS up-regulated Pin-1, phosphatase A2 (PP2A) expression, induced p66^Shc-Ser³⁶ phosphorylation, and facilitated p66^Shc mitochondrial translocation, thus leading to superoxide anion (O2⁻) generation, mitochondrial cytochrome c release, active caspase 3 over-expression and cell viability inhibition. Importantly, propofol was shown to down-regulate LPS-induced PP2A expression, limit p66^Shc mitochondrial translocation, decrease O2⁻ generation, inhibit mitochondrial cytochrome c release, reduce active caspase 3 expression, and recover cells viability, while propofol had no effects on LPS-induced Pin-1 expression and p66^Shc-Ser³⁶ phosphorylation. Moreover, the protective effects of propofol on LPS-induced BEAS-2B cells apoptosis were similar to that of calyculin A, which is an inhibitor of PP2A. We also found that FTY720, which is an activator of PP2A, can effectively reverse the protective function of propofol. Our data illustrated that propofol could alleviate LPS-induced BEAS-2B cells oxidation and apoptosis through down-regulating PP2A expression, limiting p66^Shc-Ser³⁶ dephosphorylation and p66^Shc mitochondrial translocation, decreasing O2⁻ generation, mitochondrial cytochrome c release, activating caspase 3 expression.



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