Hypochlorite modification of high density lipoprotein: effects on cholesterol efflux from J774 macrophages

The present study was aimed at investigating effects of hypochlorite (HOCl) modification of high density lipoproteins subclass 3 (HDL3) on their abili ty for cellular cholesterol removal from permanent J774 macrophages, Our fi ndings indicate that HOCl (added as reagent or generated enzymatically by t he myeloperoxidase/H2O2/Cl- system) damages apolipoprotein A-I, the major p rotein component of HDL3, Fatty acid analysis of native and HOCl-modified H DL3 revealed that unsaturated fatty acids in both major lipid subclasses (p hospholipids and cholesteryl eaters) are targets for HOCl attack. HOCl modi fication resulted in impaired HDL3-mediated cholesterol efflux from J774 ce lls, regardless of whether reagent or enzymatically generated HOCl was used to modify the lipoprotein, Decreased cholesterol efflux was also observed after HOCl modification of reconstituted HDL particles, Impairment of chole sterol efflux from macrophages was noticed at low and physiologically occur ring HOCl concentrations. (C) 1999 Federation of European Biochemical Socie ties.