HYDROXYL RADICAL ATTACK OF LOW-DENSITY-LIPOPROTEIN DECREASES ITS CELLULAR CATABOLISM IN THE ABSENCE OF SIGNIFICANT LIPID-PEROXIDATION

Low density lipoprotein (LDL) has been submitted to oxidative modifica tion induced by gamma radiolysis of water under conditions generating either hydroxyl radical (OH .) alone, or a mixture of superoxide anion and OH .. Treatment of LDL with hydroxyl radical alone did not lead t o significant lipid peroxidation as assessed thiobarbituric acid react ive substances (TEARS) and hydroperoxide measurement induced only very small change in the electrophoretic mobility of the particle. In cont rast, superoxide and hydroxyl radical mixture induced a dose-dependent increase in lipid peroxidation, with a marked elevation of the negati ve net charge of the LDL. However, in both cases, a similar reduction of the uptake and degradation of modified LDL by the apo B/E receptor pathway of human fibroblasts was observed. This suggests that factors other than lipid peroxidation could play a role in LDL modification an d influence their cellular metabolism. (C) 1995 Academic Press, Inc.