OXIDATION OF HIGH-DENSITY-LIPOPROTEINS - II - EVIDENCE FOR DIRECT REDUCTION OF LIPID HYDROPEROXIDES BY METHIONINE RESIDUES OF APOLIPOPROTEINS AI AND AII

Human high density lipoproteins (HDL) can reduce cholesteryl ester hyd roperoxides to the corresponding hydroxides (Sattler W,, Christison J, K,, and Stocker, R. (1995) Free Radical Biol, & Med. 18, 421-429), He re we demonstrate that this reducing activity extended to hydroperoxid es of phosphatidylcholine, was similar in HDL2 and HDL3, was independe nt of arylesterase and lecithin:cholesteryl acyltransferase activity, was unaffected by sulfhydryl reagents, and was expressed by reconstitu ted particles containing apoAI, or apoAII only, as well as isolated hu man apoAI, Concomitant with the reduction of lipid hydroperoxides spec ific oxidized forms of apoAI and apoAII formed in blood-derived and re constituted HDL, Similarly, specific oxidized forms of apoAI accumulat ed upon treatment of isolated apoAI with authentic cholesteryl linolea te hydroperoxide, These specific oxidized forms of apoAI and apoAII ha ve been shown previously to contain Met sulfoxide (Met(O)) at Met resi dues and are also formed when HDL is exposed to Cu2+ Or soybean lipoxy genase, Lipid hydroperoxide reduction and the associated formation of specific oxidized forms of apoAI and apoAII were inhibited by solubili zing HDL with SDS or by pretreatment of HDL with chloramine T, The inh ibitory effect of chloramine T was dose-dependent and accompanied by t he conversion of specific Met residues of apoAI and apoAII into Met(O) , Canine HDL, which contains apoAI as the predominant apolipoprotein a nd which lacks the oxidation-sensitive Met residues Met(112) and Met(1 48), showed much weaker lipid hydroperoxide reducing activity and lowe r extents of formation of oxidized forms of apoAI than human HDL, We c onclude that the oxidation of specific Met residues of apoAI and apoAI I to Met(O) plays a significant role in the 2-electron reduction of hy droperoxides of cholesteryl esters and phosphatidylcholine associated with human HDL.