title: Mechanism of cellular oxidation stress induced by asymmetric dimethylarginine.
abstract: The mechanism by which asymmetric dimethylarginine (ADMA) induces vascular oxidative stress is not well understood. In this study, we utilized human umbilical vein endothelial cells (HUVEC) to examine the roles of ADMA cellular transport and the uncoupling of endothelial nitric oxide synthase (eNOS) in contributing to this phenomenon. Dihydroethidium (DHE) fluorescence was used as an index of oxidative stress. Whole cells and their isolated membrane fractions exhibited measureable increased DHE fluorescence at ADMA concentrations greater than 10 μM. ADMA-induced DHE fluorescence was inhibited by co-incubation with L-lysine, tetrahydrobiopterin (BH(4)), or L-nitroarginine methyl ester (L-NAME). Oxidative stress induced in these cells by angiotensin II (Ang II) were unaffected by the same concentrations of L-lysine, L-NAME and BH(4). ADMA-induced reduction in cellular nitrite or nitrite/nitrate production was reversed in the presence of increasing concentrations of BH(4). These results suggest that ADMA-induced DHE fluorescence involves the participation of both the cationic transport system in the cellular membrane and eNOS instead of the Ang II-NADPH oxidase pathway.
authors: Department of Pharmaceutical Sciences, University of New England, Portland, ME 04103, USA.
authors: Srinidi
authors: S
authors: Mohan
authors: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors: Ho-Leung
authors: HL
authors: Fung
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D001708:Biopterins; C018524:N,N-dimethylarginine; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester