Reduction of HDL- 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 HDLox and LDLox was investigated using specific HPLC assays for the hydroperoxides of phosphatidylcholine (PCOOH) and cholesteryllinolate (Ch18:2-OOH) and for cholesteryllinolate hydroxides (Ch18:2-OH). HDLox and LDLox were formed from the corresponding isolated native lipoproteins by controlled and limited oxidation initiated by aqueous peroxyl radicals. Incubation of HDLox or LDLox 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 HDLox-associated PCOOH and Ch18:2-OOH appeared to be slightly better substrates for PHGPx/GSH as compared to those in LDLox. Also, Ch18:2-OOH associated with HDLox but not LDLox 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.
Sattler
W
W
Biochemistry Group, Heart Research Institute, Sydney, New South Wales, Australia.
Maiorino
M
M
Stocker
R
R
D001393:Azoles / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D054833:Isoindoles; D008054:Lipid Peroxides / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D016566:Organoselenium Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000097:blood; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D010743:Phospholipids / Q000097:blood
D001393:Azoles; D002788:Cholesterol Esters; D005609:Free Radicals; D054833:Isoindoles; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016566:Organoselenium Compounds; D010713:Phosphatidylcholines; D010743:Phospholipids; C042986:ebselen; C021976:cholesteryl linoleate; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D005978:Glutathione