title: Recycling of vitamin E in human low density lipoproteins.
abstract: Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptor-dependent uptake is believed to account for cholesterol deposition in macrophage-derived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be achieved by reducing its chromanoxyl radicals, i.e., by vitamin E recycling. In this study we demonstrate that: i) chromanoxyl radicals of endogenous vitamin E and of exogenously added alpha-tocotrienol, alpha-tocopherol or its synthetic homologue with a 6-carbon side-chain, chromanol-alpha-C6, can be directly generated in human LDL by ultraviolet (UV) light, or by interaction with peroxyl radicals produced either by an enzymic oxidation system (lipoxygenase + linolenic acid) or by an azo-initiator, 2,2'-azo-bis(2,4-dimethylvaleronitrile) (AMVN; ii) ascorbate can recycle endogenous vitamin E and exogenously added chromanols by direct reduction of chromanoxyl radicals in LDL; iii) dihydrolipoic acid is not efficient in direct reduction of chromanoxyl radicals but recycles vitamin E by synergistically interacting with ascorbate (reduces dehydroascorbate thus maintaining the steady-state concentration of ascorbate); and iv) beta-carotene is not active in vitamin E recycling but may itself be protected against oxidative destruction by the reductants of chromanoxyl radicals. We suggest that the recycling of vitamin E and other phenolic antioxidants by plasma reductants may be an important mechanism for the enhanced antioxidant protection of LDL.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720.
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
authors.forename: E A
authors.initials: EA
authors.lastname: Serbinova
authors.forename: T
authors.initials: T
authors.lastname: Forte
authors.forename: G
authors.initials: G
authors.lastname: Scita
authors.forename: L
authors.initials: L
authors.lastname: Packer
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D002338:Carotenoids / Q000097:blood; D002839:Chromans / Q000097:blood; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008077:Lipoproteins, LDL / Q000097:blood*; D008084:Lipoxygenase / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000097:blood*; D019207:beta Carotene
chemical_list: D002839:Chromans; D016166:Free Radical Scavengers; D008042:Linolenic Acids; D008077:Lipoproteins, LDL; D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; D008063:Thioctic Acid; C015144:dihydrolipoic acid; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D008084:Lipoxygenase; D001205:Ascorbic Acid