title: Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress.
abstract: Exposure of endothelial cells to oxidized low-density lipoprotein (oxLDL) leads to diverse cellular effects, including induction of the intracellular antioxidant GSH. It is not known whether lipid-or protein-derived oxidation products cause GSH induction and whether this involves increased activity of the key enzyme in its synthesis, glutamate-cysteine ligase (GCL). Furthermore, the effect of oxLDL exposure on the cell's ability to combat oxidative stress has not been previously examined. In the present study we found that, in bovine aortic endothelial cells, LDL or 1-palmitoyl-2-arachidonyl phosphatidylcholine oxidized by different reactive oxygen and nitrogen species induced GSH synthesis. However, prevention of GSH synthesis during exposure to oxLDL caused extensive cell death. The mediator causing GSH induction was shown to be a polar lipid and resulted in the increased activity of GCL as well as increased protein levels of the regulatory subunit of GCL. Pretreatment with both oxLDL and the polar lipid subfraction of the oxLDL protected cells against the toxicity of 2,3-dimethoxynaphthoquinone (DMNQ), a superoxide- and H(2)O(2)-forming compound. The potential of a low level of lipid peroxidation products to initiate cytoprotective pathways are discussed.
authors.affiliation: Department of Pathology, Molecular and Cellular Division, School of Public Health, University of Alabama at Birmingham, Volker Hall G019, 1670 University Boulevard, Birmingham, AL 35295-0019, U.S.A.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Moellering
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Levonen
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Go
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Dale A
authors.initials: DA
authors.lastname: Dickinson
authors.forename: Henry Jay
authors.initials: HJ
authors.lastname: Forman
authors.forename: Victor M
authors.initials: VM
authors.lastname: Darley-Usmar
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D008077:Lipoproteins, LDL; D010742:Phospholipid Ethers; C099252:oxidized low density lipoprotein; D013481:Superoxides; C004532:quinone; C043051:1-O-hexadecyl-2-arachidonyl-sn-glycero-3-phosphocholine; D006861:Hydrogen Peroxide; D005978:Glutathione