The participation of nitric oxide in cell free-and its restriction of macrophage-mediated oxidation of low-density lipoprotein

W Jessup, D Mohr, SP Gieseg, RT Dean… - Biochimica et Biophysica …, 1992 - Elsevier
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1992Elsevier
The potential role of nitric oxide radical (NO·) in macrophage-mediated oxidation and
conversion of human low density lipoprotein (LDL) to a high-uptake form was examined by
exposing LDL to aerobic solutions to either NO· or 3-morpholinosydnonimine-hydrochloride
(SIN-1, a compound that spontaneously forms NO· and superoxide anion radical) or to
mouse peritoneal macrophages in the presence and absence of modulators of cellular NO·
synthesis. Incubation with NO· alone caused oxidation of LDL's ubiquinol-10 and …
Abstract
The potential role of nitric oxide radical (NO ·) in macrophage-mediated oxidation and conversion of human low density lipoprotein (LDL) to a high-uptake form was examined by exposing LDL to aerobic solutions to either NO · or 3-morpholinosydnonimine-hydrochloride (SIN-1, a compound that spontaneously forms NO · and superoxide anion radical) or to mouse peritoneal macrophages in the presence and absence of modulators of cellular NO · synthesis. Incubation with NO · alone caused oxidation of LDL's ubiquinol-10 and accumulation of small amounts of lipid hydroperoxidases, but failed to form any high-uptake ligand for endocytosis by macrophages and did not alter the LDL particle charge or the integrity of apoB. Exposure of LDL to SIN-1 resulted in complete consumption of all antioxidants and substantial formation of lipid hydroperoxidases, but again had little effect on the lipoprotein particle charge or generation of high-uptake form. Preincubation of macrophages with interferon-γ increased the cells ability to generate reactive nitrogen metabolites. The extent of cell-mediated oxidation of LDL and the generation of high-uptake LDL was substantial in resident cells in which NO · synthesis was barely detectable, depressed in cells active in NO · synthesis and restored when NO · synthesis was suppressed by the arginine analogue, NMMA. These results suggest that, while longer with superoxide anion radical, NO · can oxidize LDL, its synthesis is not required for macrophage-mediated oxidation of LDL in vitro; rather it exerts a protective role in preventing oxidative LDL modification by macrophages.
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