出版社:American Society for Biochemistry and Molecular Biology
摘要:Oxidative modification of low density lipoprotein (LDL) has been suggested as a causal step in atherosclerosis, and both redox-active transition metal ions and superoxide (O2.-) have been implicated in this process. In order to determine the mechanisms of metal ion-dependent oxidation of LDL in the presence of O2.-, LDL was exposed to hypoxanthine (HX) and purified xanthine oxidase (XO) without and with added CuCl2 or Fe(3+)-citrate. Production of O2.- and hydrogen peroxide (H2O2) at pH 7.4 by the HX/XO system in the absence of metal ions was not sufficient to oxidize LDL. Preincubation of LDL with Cu2+ or Fe(3+)-citrate with subsequent removal of metal ions not tightly bound to the lipoprotein did not enable the HX/XO system to oxidize LDL. However, incubation of LDL with HX/XO and Cu2+ resulted in extensive modification of LDL. Exposure of LDL to Cu2+ alone also led to extensive modification, although the LDL was initially free of detectable amounts of lipid hydroperoxides (LOOH), i.e.,