REDUCTION OF HDL-ASSOCIATED AND LDL-ASSOCIATED CHOLESTERYLESTER AND PHOSPHOLIPID HYDROPEROXIDES BY PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE AND EBSELEN (PZ-51)

The reaction of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and Ebselen with phospholipid and cholesterylester hydroperoxides associated with HDL(ox) and LDL(ox) was investigated using specific HPLC assays for the hydroperoxides of phosphatidylcholine (PCOOH) and cholesteryllinolate (Ch18:2-OOH) and for cholesteryllinolate hydroxides (Ch18:2-OH). HDL(ox) and HDL(ox) were formed from the corresponding isolated native lipoproteins by controlled and limited oxidation initiated by aqueous peroxyl radicals. Incubation of HDL(ox) or LDL(ox) in the presence of PHGPx/GSH or Ebselen/GSH resulted in rapid degradation of both classes of lipid hydroperoxides, with equimolar amounts of Ch18:2-OH formed from Ch18:2-OOH. No pronounced differences were observed between PCOOH and Ch18:2-OOH in terms of substrate specificity, whereas HDL(ox)-associated PCOOH and Ch18:2-OOH appeared to be slightly better substrates for PHGPx/GSH as compared to those in LDL(ox). Also, Ch18:2-OOH associated with HDL(ox) but not LDL(ox) were reduced by Ebselen or GSH alone. These in vitro findings indicate that the enzymatic PHGPx/GSH and the nonenzymatic Ebselen/GSH systems can efficiently reduce hydroperoxides of phospholipids and cholesterylesters associated with intact lipoproteins. (C) 1994 Academic Press, Inc.