期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 40, 期 5, 页码 920-928出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2007.10.027
关键词
oxLDL; arginine metabolism; cationic amino acid transporter 1; eNOS; cholesterol
The action of oxidatively modified low-density lipoprotein on vascular endothelial cells has been proposed to be a crucial process leading to endothelial dysfunction and atherogenesis. However, the biochemical mechanism for such action is not clear. We have previously shown that arginine uptake and metabolism are major determinants of endothelial function in heart failure and hypertension. In the present study we therefore aimed to assess the effects of oxidized LDL, a major pro-atherogenic molecule, on endothelial L-arginine metabolism and its uptake. Endothelial cells were exposed to oxidized LDL or native LDL for 24h, and the resultant effects on (1) the intracellular content of arginine and its major metabolites including citrulline, N-G-hydrOXY-L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine and ornithine, (2) [H-3]-L-arginine uptake and, (3) the pattern of distribution of cationic amino acid transporter 1, the principal L-arginine transporter, by confocal microscopy. Oxidized LDL (100,mu g/mL) reduced intracellular arginine and N-G-hydroxy-L-arginine contents by 56 and 71% (P<0.05), respectively, with a concomitant 205% increase in ADMA (P < 0.05). In conjunction, oxidized LDL reduced endothelial uptake of [H-3]-arginine by 60%. Furthermore, incubation of endothelial cells with oxLDL led to internalization of cationic amino acid transporter 1. We demonstrate a novel mechanism, reduced L-arginine transport, by which oxidized LDL impairs the ability of the endothelium to generate nitric oxide. (C) 2007 Elsevier Ltd. All rights reserved.
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