title: Oxidation of high density lipoproteins. II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII.
abstract: Human high density lipoproteins (HDL) can reduce cholesteryl ester hydroperoxides to the corresponding hydroxides (Sattler W., Christison J. K., and Stocker, R. (1995) Free Radical Biol. & Med. 18, 421-429). Here we demonstrate that this reducing activity extended to hydroperoxides of phosphatidylcholine, was similar in HDL2 and HDL3, was independent of arylesterase and lecithin:cholesteryl acyltransferase activity, was unaffected by sulfhydryl reagents, and was expressed by reconstituted particles containing apoAI or apoAII only, as well as isolated human apoAI. Concomitant with the reduction of lipid hydroperoxides specific oxidized forms of apoAI and apoAII formed in blood-derived and reconstituted HDL. Similarly, specific oxidized forms of apoAI accumulated upon treatment of isolated apoAI with authentic cholesteryl linoleate hydroperoxide. These specific oxidized forms of apoAI and apoAII have been shown previously to contain Met sulfoxide (Met(O)) at Met residues and are also formed when HDL is exposed to Cu2+ or soybean lipoxygenase. Lipid hydroperoxide reduction and the associated formation of specific oxidized forms of apoAI and apoAII were inhibited by solubilizing HDL with SDS or by pretreatment of HDL with chloramine T. The inhibitory effect of chloramine T was dose-dependent and accompanied by the conversion of specific Met residues of apoAI and apoAII into Met(O). Canine HDL, which contains apoAI as the predominant apolipoprotein and which lacks the oxidation-sensitive Met residues Met112 and Met148, showed much weaker lipid hydroperoxide reducing activity and lower extents of formation of oxidized forms of apoAI than human HDL. We conclude that the oxidation of specific Met residues of apoAI and apoAII to Met(O) plays a significant role in the 2-electron reduction of hydroperoxides of cholesteryl esters and phosphatidylcholine associated with human HDL.
authors.affiliation: Biochemistry Group, The Heart Research Institute, Sydney New South Wales 2050, Adelaide South Australia 5000, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Garner
authors.forename: A R
authors.initials: AR
authors.lastname: Waldeck
authors.forename: P K
authors.initials: PK
authors.lastname: Witting
authors.forename: K A
authors.initials: KA
authors.lastname: Rye
authors.forename: R
authors.initials: R
authors.lastname: Stocker
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D001054:Apolipoproteins A / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism*; D008956:Models, Chemical; D010084:Oxidation-Reduction
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D008715:Methionine; D000217:Acyltransferases; C020597:glycerophospholipid-cholesterol acyltransferase