high-uptake form for macrophages

Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure ofLDL to reagent hypochlorite (NaOCl) at 4°C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDLassociated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations ofNaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B100 quantitatively represented the major target, scavenging some 68 % of the NaOCl added, with tryptophan and cysteine together