title: Propofol protects human umbilical vein endothelial cells from cisplatin-induced injury.
abstract: The anticancer drug cisplatin can up-regulate endothelial adhesion molecule expression, and trigger vascular endothelial injury. Propofol, an intravenous anesthetic, can inhibit endothelial adhesion molecule expression in some situations. Here, we explored whether and how propofol improved cisplatin-induced up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells. Compared with control group, cisplatin reduced endothelial nitric oxide synthase dimer/monomer ratio, activated protein kinase C and enhanced endothelial nitric oxide synthase-Thr495 phosphorylation, decreased nitric oxide production, augmented intercellular adhesion molecule 1 expression and monocyte-endothelial adhesion. These cisplatin-mediated effects were attenuated by propofol treatment. Nω-Nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, inhibited the effect of propofol on cisplatin-induced intercellular adhesion molecule 1 expression. Propofol improved cisplatin-mediated tetrahydrobiopterin reduction and nitrotyrosine overexpression. Compared with control group, cisplatin and PMA, a protein kinase C activator, both increased endothelial nitric oxide synthase-Thr495 phosphorylation, while propofol and GFX, a protein kinase C inhibitor, both decreased cisplatin-induced endothelial nitric oxide synthase-Thr495 phosphorylation. Our data indicated that propofol, via reducing cisplatin-induced endothelial nitric oxide synthase uncoupling and endothelial nitric oxide synthase-Thr495 phosphorylation, restored nitric oxide production, intercellular adhesion molecule 1 expression and monocyte-endothelial interaction.
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. Electronic address: natalie7901@126.com.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D002945:Cisplatin; D015742:Propofol
keywords: Cisplatin; Endothelium; ICAM-1; Propofol; eNOS