Document Detail

Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress.
MedLine Citation:
PMID:  11829739     Owner:  NLM     Status:  MEDLINE    
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.
Douglas R Moellering; Anna-Liisa Levonen; Young-Mi Go; Rakesh P Patel; Dale A Dickinson; Henry Jay Forman; Victor M Darley-Usmar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  362     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-06     Completed Date:  2002-03-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  51-9     Citation Subset:  IM    
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.
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MeSH Terms
Benzoquinones / pharmacology*
Cells, Cultured
Endothelium, Vascular / cytology,  drug effects,  metabolism*
Glutathione / biosynthesis*
Hydrogen Peroxide / pharmacology
Lipoproteins, LDL / physiology*
Oxidative Stress / drug effects*
Phospholipid Ethers / pharmacology*
Superoxides / metabolism
Grant Support
Reg. No./Substance:
0/Benzoquinones; 0/Lipoproteins, LDL; 0/Phospholipid Ethers; 0/oxidized low density lipoprotein; 106-51-4/benzoquinone; 11062-77-4/Superoxides; 6931-56-2/1-O-hexadecyl-2-arachidonyl-sn-glycero-3-phosphocholine; 70-18-8/Glutathione; 7722-84-1/Hydrogen Peroxide

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