title: Propofol dose-dependently reduces tumor necrosis factor-alpha-Induced human umbilical vein endothelial cell apoptosis: effects on Bcl-2 and Bax expression and nitric oxide generation.
abstract: We investigated whether propofol can inhibit tumor necrosis factor (TNF)-alpha-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs). Isolated HUVECs were cultured in Dulbecco's modified Eagle medium supplemented with 20% bovine calf serum. HUVECs in untreated and propofol control groups were cultured at 37 degrees C for 24.5 h. HUVECs in the TNF treatment groups were initially cultured for 30 min in the presence of TNF or various concentrations of propofol, respectively, which were then cultured for 24 h with the addition of TNF at 40 ng/mL in the medium. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and confirmed by electron microscopy. The antiapoptotic Bcl-2 and proapoptotic Bax protein expressions were measured by immunocytochemical analysis. TNF stimulation resulted in a reduced Bcl-2/Bax ratio and increased apoptotic index (AI: percentage of apoptotic cells) in HUVECs. Propofol, at concentrations >/=12 muM, significantly (P < 0.001) and dose-dependently attenuated TNF-induced increase in AI and decrease in Bcl-2/Bax ratio. This was accompanied by increases in nitric oxide production. There is an inverse correlation between the ratio of Bcl-2/Bax expression and AI (P = 0.0009). These results suggest that propofol, at clinical relevant concentrations, can reduce TNF-induced HUVEC apoptosis.
authors.affiliation: *Department of Anesthesiology, Renmin Hospital, Wuhan University; †Department of Pathophysiology, Faculty of Medicine, Wuhan University, Wuhan, People's Republic of China; ‡Centre for Anesthesia & Analgesia, Department of Pharmacology & Therapeutics, The University of British Columbia, Vancouver; and §The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: David M
authors.initials: DM
authors.lastname: Ansley
authors.forename: Jingping
authors.initials: J
authors.lastname: Ouyang
authors.forename: David J
authors.initials: DJ
authors.lastname: Granville
authors.forename: Yinping
authors.initials: Y
authors.lastname: Li
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Xia
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Zhou
authors.forename: Xian-Yi
authors.initials: XY
authors.lastname: Liu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D051028:bcl-2-Associated X Protein
chemical_list: D018686:Anesthetics, Intravenous; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D015742:Propofol