The role of alpha-tocopherol as a peroxyl radical scavenger in human low density lipoprotein.
It is thought that the oxidation of low density lipoprotein (LDL) plays a key role in the pathogenesis of atherosclerosis. It is well known that lipid peroxidation reactions are propagated by peroxyl radicals and it follows, therefore, that the capacity of an individual LDL particle to scavenge these oxidants may be an important indicator of its atherogenic potential. There are several components within LDL which scavenge peroxyl radicals including chain breaking antioxidants and amino acids on the protein. It is not clear at present which of these antioxidants is most important. In attempting to address the question we have used a simple method for the measurement of the total capacity of the LDL particle to scavenge peroxyl radicals. This assay depends upon the ability of antioxidants in LDL to inhibit the peroxyl radical dependent oxidation of luminol. We have found that approximately 80% of the antioxidant capacity of LDL, isolated from a number of donors, could be accounted for by the alpha-tocopherol present in the samples. We have compared these results with those obtained when the identical samples of LDL were oxidized with copper and found, as reported by others, a wide range in the susceptibility of the different LDL preparations to oxidation by this transition metal. We suggest that this variability is unlikely to be due to differences in the ability of an LDL particle to scavenge peroxyl radicals.
Department of Biochemical Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.
D
D
Smith
V J
VJ
O'Leary
V M
VM
Darley-Usmar
D000328:Adult; D000578:Amidines; D003300:Copper; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000302:isolation & purification; D008165:Luminol; D008875:Middle Aged; D010545:Peroxides; D014810:Vitamin E / Q000494:pharmacology*
D000578:Amidines; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D010545:Peroxides; D014810:Vitamin E; C049375:perhydroxyl radical; D008165:Luminol; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper