Inhibition of low‐density lipoprotein oxidation by nitric oxide Potential role in atherogenesis

Abstract

The effects of nitric oxide ('NO) and nitrovasodilators on the oxidation of low-density lipoprotein (LDL) have been studied. S-Nitroso-Nacetylpenicillamine (SNAP) and sodium nitroprusside (SNP) inhibited Cu 2÷-and 2,2'-azobis-2-amidinopropane hydrochloride-dependent oxidation of LDL as monitored by oxygen consumption and the formation of thiobarbituric acid-reactive substances, conjugated dienes, and lipid hydroperoxides. In the case of SNP, inhibition of LDL oxidation occurred only when the incubation mixture was irradiated with visible light. SNAP, however, exerted a dose-dependent inhibition of CuZ÷-catalyzed oxidation of LDL even in the dark. Addition of "NO dissolved in deoxygenated buffer also inhibited the progression of LDL oxidation. Mouse peritoneal macrophages were less able to degrade LDL that had been oxidized in the presence of SNAR Using an "NO electrode, it was estimated that a continuous production of'NO (~< 760 nM/min) could retard the progression of LDL oxidation. We propose that "NO can inhibit LDL oxidation by acting as a chain-breaking antioxidant that is capable of scavenging carbon-centered and peroxyl radicals. Biological implications of this novel °NO antioxidant property are discussed in relation to atherogenesis and contrasted to the prooxidant property of "NO when generated in the presence of superoxide.

Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury

“…The former effect is attributed to the formation of the toxic peroxynitrite after reaction with O 2 Ϫ [11]. The latter effect is not well defined, although inhibition of oxidative killing of Chinese hamster V79 cells [27], attenuation of low-density lipoprotein oxidation [28], and prevention of myocardial ischemiareperfusion injury [10] have been demonstrated. Our goal was to understand the interactive role of NO and ROI in cellular events that culminate in PMN-mediated EC injury.…”

Dualism of Oxidized Lipoproteins in Provoking and Attenuating the Oxidative Burst in Macrophages: Role of Peroxisome Proliferator-Activated Receptor-γ

“…Human monocytes were isolated from buffy coats of healthy donors as previously described (36). After Ficoll gradient centrifugation, monocytes were cultured under adherent conditions in six-well plates in RPMI 1640 supplemented with 10% human serum AB, 1% nonessential amino acids, 1 mM sodium pyruvate, 2 mM L-glutamine, 100 U/ml penicillin, and 100 FIGURE 1.…”

The Cytotoxicity of Nitroxyl: Possible Implications for the Pathophysiological Role of NO

“…In conprotection against AS-mediated cytotoxicity. Treat-trast, NO can protect cells from damage caused by reacment of V79 cells with L-buthionine sulfoximine to re-tive oxygen species (ROS) (4-6), as a result of different duce intracellular glutathione markedly enhanced AS chemical reactions than those involving RNOS (7)(8)(9)(10).…”