title: 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), p66shcand mitochondrial p66shcexpression, increased p66shc-Ser36phosphorylation, and O2·- accumulation. More importantly, although propofol had no effect on 15 mm glucose-induced p66shc-Ser36phosphorylation and pin-1 expression, propofol could downregulated PP2A expression and p66shcexpression 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-Ser36dephosphorylation and mitochondrial p66shcexpression.
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000009:adverse effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013481:Superoxides; D054648:Protein Phosphatase 2; D005947:Glucose; D010100:Oxygen; D015742:Propofol
keywords: 
  reactive oxygen species
  ; high glucose; propofol