ESTERIFICATION OF CHOLESTEROL OXIDATION-PRODUCTS AND THEIR EFFECTS ON THE RATE OF CHOLESTEROL ESTERIFICATION IN MACROPHAGES

Effects of cholesterol (CH) autooxidation products on incorporation of C-14-oleate into cholesteryl esters (CE) and their possible esterification were studied in cultivated mice peritoneal macrophages (MPM). 25 Mg/ml of purified CH and 25 Mg/ml of autooxidized CH stimulated (4- and 17-fold, respectively) the cholesterol esterification in MPM. In presence of 4 Mg/ml 25-hydroxy CH or the mixture of 4 Mg/ml 7-alpha-, 7-beta-hydroxy CH and 7-keto CH incorporation of oleate into cellular CE was increased 20- and 4-fold, respectively. 4 Mg/ml concentration of cholestane-3-beta, 5-alpha, 6-beta-friol caused no effects. Mono- and diesters of C-14-hydroxy CH were found after 8 hrs incubation of the steroid with MPM. Incorporation of C-14-25 hydroxy CH into its esters occurred at the rate, which exceeded 6-7-fold the C-14-CH incorporation into CE. Esterification of 7-alpha, 7-beta-hydroxyCH and 7-ketoCH was studied, 0.52% label of the total cell sterols radioactivity was detected in the fraction of nonpolar steroids. C-14-cholestane-3-beta,5-alpha,6-beta-triol was not esterified in MPM. The stimulating effects of 25-hydroxyCH on oleate incorporation into CE and its esterification in MPM were inhibited in presence of 10 Mg/ml progesterone, an inhibitor of acyl-CoA:cholesterol acyltransferase activity. Induction of CE formation in MPM by means of choltransferase activity. Induction of CE formation in MPM by means of choltransferase activity. Induction of CE formation in MPM by means of cholesterol oxidation products may be responsible for development of foam cells, while esterification of polar steroids in cells appears to be of importance in decrease of their toxic and metabolic effects.