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Mechanism of Cellular Oxidation Stress Induced by Asymmetric Dimethylarginine
Department of Pharmaceutical Sciences, University of New England, Portland, ME 04103, USA
Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
* Author to whom correspondence should be addressed.
Received: 2 May 2012; in revised form: 7 June 2012 / Accepted: 13 June 2012 / Published: 18 June 2012
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 (BH4), 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 BH4. ADMA-induced reduction in cellular nitrite or nitrite/nitrate production was reversed in the presence of increasing concentrations of BH4. 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.
Keywords: asymmetric dimethylarginine; tetrahydrobiopterin; endothelial nitric oxide synthase; oxidative stress
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MDPI and ACS Style
Mohan, S.; Fung, H.-L. Mechanism of Cellular Oxidation Stress Induced by Asymmetric Dimethylarginine. Int. J. Mol. Sci. 2012, 13, 7521-7531.
Mohan S, Fung H-L. Mechanism of Cellular Oxidation Stress Induced by Asymmetric Dimethylarginine. International Journal of Molecular Sciences. 2012; 13(6):7521-7531.
Mohan, Srinidi; Fung, Ho-Leung. 2012. "Mechanism of Cellular Oxidation Stress Induced by Asymmetric Dimethylarginine." Int. J. Mol. Sci. 13, no. 6: 7521-7531.