title: Arsenic induces apoptosis of human umbilical vein endothelial cells through mitochondrial pathways.
abstract: To clarify the molecular mechanisms through which arsenic causes injuries to blood vessels, we analyzed the effects of sodium arsenite (NaAsO(2)) on the apoptosis of human umbilical vein endothelial cells (HUVECs), mitochondrial membrane potential (Delta Psi m), intracellular reactive oxygen species (ROS), and the expression of the related genes. HUVECs apoptosis increased and Delta Psi m decreased in a dose-dependent manner following arsenic treatment. Intracellular ROS showed 2 phase alterations: a slight decrease with low levels of arsenic (5 and 10 microM) treatment; but a sharp increase at higher concentrations (>or=20 microM). The arsenic-induced cell apoptosis and intracellular ROS were blocked by the addition of the antioxidant N-acetyl-L-cysteine (NAC). The mRNAs of superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) increased strikingly when cells were treated with a low concentration of NaAsO(2) (5 microM) and the level of induction was decreased with higher concentrations of arsenic treatment. Based on the results, we suggest that the decrease of Delta Psi m caused by arsenic and the resulting cell apoptosis may contribute to the injuries of blood vessel in arsenism. The decrease in intracellular ROS and the increase in SOD2 and NQO1 expressions observed when HUVECs were treated with low concentration of NaAsO(2), suggest the role of the two enzymes in protecting HUVECs from injuries of arsenic exposure.
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, People's Republic of China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.forename: Yudan
authors.initials: Y
authors.lastname: Wei
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D051336:Mitochondrial Membranes / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects*; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D018053:Arsenites; D004791:Enzyme Inhibitors; D016660:NAD(P)H Dehydrogenase (Quinone); D012313:RNA; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C017947:sodium arsenite; C441642:SOD3 protein, human; C447479:NQO1 protein, human