title: Propofol ameliorates endothelial inflammation induced by hypoxia/reoxygenation in human umbilical vein endothelial cells: Role of phosphatase A2.
abstract: Hypoxia/reoxygenation (H/R) induces endothelial inflammation with augmentation of endothelial adhesion molecules over-expression. Propofol was reported to attenuate endothelial adhesion molecule expression in some situations. Here, we examined the molecular mechanism for how propofol restored H/R-mediated up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells (HUVECs). Compared with the control group, H/R up-regulated expression of Pin-1 and PP2A, increased p66(Shc)-Ser(36) phosphorylation, induced p66(Shc) mitochondrial translocation, O2(-) accumulation and NF-κB activation, and decreased eNOS-Ser(1177) phosphorylation and nitric oxide (NO) production, thus up-regulating expression of endothelial adhesion molecules and increasing mononuclear-endothelial interaction. More importantly, except that propofol had no effect on H/R-induced p66(Shc)-Ser(36) phosphorylation, most of H/R-mediated changes were alleviated by propofol, resulting in the reduction of endothelial adhesion molecules expression and mononuclear-endothelial adhesion. Moreover, we demonstrated the protective effect of propofol on H/R-induced endothelial inflammation 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 propofol down-regulated PP2A expression, leading to reduced dephosphorylation of p66(Shc)-Ser(36) and eNOS-Ser(1177), which is associated with ROS accumulation and NO reduction, resulting in inhibition of endothelial adhesion molecule expression and mononuclear-endothelial interaction.
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address: miao_chh@126.com.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013481:Superoxides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013481:Superoxides; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054648:Protein Phosphatase 2; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; D015742:Propofol
keywords: Endothelial; Hypoxia/reoxygenation; Propofol