In vitro cell injury by oxidized low density lipoprotein involves lipid hydroperoxide-induced formation of alkoxyl, lipid, and peroxyl radicals
| Autor: | M D Coffey, S M Colles, R A Cole, G M Chisolm |
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| Rok vydání: | 1995 |
| Předmět: |
Azoles
Free Radicals Arteriosclerosis Radical Iron Probucol Isoindoles Lipid peroxidation chemistry.chemical_compound Organoselenium Compounds medicine Humans Lipoprotein oxidation Cells Cultured chemistry.chemical_classification Reactive oxygen species Arachidonic Acid Ebselen Chloroquine General Medicine Peroxides Lipoproteins LDL Cholesterol chemistry Biochemistry Alcohols Toxicity lipids (amino acids peptides and proteins) Lipid Peroxidation Oxidation-Reduction Intracellular medicine.drug Research Article |
| Zdroj: | The Journal of clinical investigation. 96(4) |
| ISSN: | 0021-9738 |
| Popis: | Mounting evidence supports current theories linking lipoprotein oxidation to atherosclerosis. We sought the cellular biochemical mechanism by which oxidized LDL inflicts cell injury. Inhibitors of candidate pathways of cell death were used to treat human fibroblast target cells exposed to oxidized LDL.. Ebselen, which degrades lipid hydroperoxides, inhibited oxidized LDL toxicity, consistent with our recent report that 7 beta-hydroperoxycholesterol (7 beta-OOH chol) is the major cytotoxin of oxidized LDL. Intracellular chelation of metal ions inhibited, while preloading cells with iron enhanced, toxicity, Inhibition of oxidized LDL and 7 beta-OOH chol toxicity by 2-keto-4-thiolmethyl butyric acid, a putative alkoxyl radical scavenger and by vitamin E, probucol and diphenylphenylenediamine, putative scavengers of peroxyl radicals was consistent with the involvement of these radicals in the lethal sequence. Cell death was thus postulated to occur due to lipid peroxidation via a sequence involving lipid hydroperoxide-induced, iron-mediated formation of alkoxyl, lipid, and peroxyl radicals. Pathways involving other reactive oxygen species, new protein synthesis, or altered cholesterol metabolism were considered less likely, since putative inhibitors failed to lessen toxicity. Understanding the mechanism of cell injury by oxidized LDL and its toxic moiety, 7 beta-OOH chol, may indicate specific interventions in the cell injury believed to accompany vascular lesion development. |
| Databáze: | OpenAIRE |
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