title: Superoxide generated by lysophosphatidylcholine induces endothelial nitric oxide synthase downregulation in human endothelial cells.
abstract: We examined the mechanism through which lysophosphatidylcholine (LPC) induces endothelial nitric oxide (eNOS) downregulation. Human umbilical vein endothelial cells (HUVECs) were treated with LPC (50-150 microM) for 0.5-2 h or the reactive oxygen species (ROS) donors, xanthine/xanthine oxidase (X/XO), 1,4-hydroquinone (HQ) or tert-butylhydroperoxide (TBHP) for 2 h. Protein levels of eNOS, superoxide dismutase1 (SOD1), catalase, and phospho-extracellular signal regulated kinase 1/2 (pERK 1/2) were assessed using immunoblotting. LPC treatment reduced SOD1 levels but increased catalase levels. The superoxide donors X/XO and HQ showed similar effects. The hydroperoxide donor TBHP increased SOD1 levels but did not change catalase levels. LPC concentration- and time-dependently decreased eNOS levels, but this effect was blocked by antioxidants and SOD and potentiated by the SOD1 inhibitor, ammonium tetrathiomolybdate. LPC and X/XO inhibited ERK1/2 phosphorylation, whereas TBHP stimulated phosphorylation. Taken together, these data indicate that LPC induces superoxide overload in HUVECs via SOD1 inhibition and downregulates phospho-ERK1/2 and eNOS levels.
authors.affiliation: Department of Physiology and Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Shinkyu
authors.initials: S
authors.lastname: Choi
authors.forename: Seonghee
authors.initials: S
authors.lastname: Park
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Liang
authors.forename: Ji Aee
authors.initials: JA
authors.lastname: Kim
authors.forename: Suk Hyo
authors.initials: SH
authors.lastname: Suh
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008982:Molybdenum / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D008244:Lysophosphatidylcholines; D013481:Superoxides; D008982:Molybdenum; C020809:tetrathiomolybdate; D020122:tert-Butylhydroperoxide; D002374:Catalase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C031927:hydroquinone