title: Propofol inhibits LPS-induced apoptosis in lung epithelial cell line, BEAS-2B.
abstract: 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 p66Shc-Ser36phosphorylation, and facilitated p66Shcmitochondrial 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 p66Shcmitochondrial 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 p66Shc-Ser36phosphorylation. 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 p66Shc-Ser36dephosphorylation and p66Shcmitochondrial translocation, decreasing O2-generation, mitochondrial cytochrome c release, activating caspase 3 expression.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China. Electronic address: mzjianghong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015742:Propofol / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D015742:Propofol
keywords: LPS; PP2A; Propofol; p66(Shc)