REQUIREMENT FOR, PROMOTION, OR INHIBITION BY ALPHA-TOCOPHEROL OF RADICAL-INDUCED INITIATION OF PLASMA-LIPOPROTEIN LIPID-PEROXIDATION

Citation
J. Neuzil et al., REQUIREMENT FOR, PROMOTION, OR INHIBITION BY ALPHA-TOCOPHEROL OF RADICAL-INDUCED INITIATION OF PLASMA-LIPOPROTEIN LIPID-PEROXIDATION, Free radical biology & medicine, 22(1-2), 1997, pp. 57-71
Citations number
56
Categorie Soggetti
Biology
ISSN journal
08915849
Volume
22
Issue
1-2
Year of publication
1997
Pages
57 - 71
Database
ISI
SICI code
0891-5849(1997)22:1-2<57:RFPOIB>2.0.ZU;2-X
Abstract
alpha-Tocopherol (alpha-TOH), generally regarded as the most important lipid-soluble, chain-breaking antioxidant in human plasma, can also b e a pro-oxidant in isolated low-density lipoprotein (LDL) (Bowry V. W. ; Stocker R. J. Am. Chem. Sec. 115:6029-6044; 1993). Here we examined whether this pro-oxidant activity of alpha-TOH is of more general rele vance. We compared the oxidizability of lipid hydroperoxide-free, in v ivo or in vitro alpha-TOH-depleted LDL and high-density lipoprotein (H DL), as well as plasma reconstituted with alpha-TOH-depleted lipoprote ins, with that of the corresponding native and alpha-TOH-supplemented samples, using water- and lipid-soluble peroxyl radicals (ROO .), hydr oxyl radicals (. OH), Cu2+, the transition metal-containing Ham's F-10 medium, soybean 15-lipoxygenase, and horseradish peroxidase as oxidan ts. Lipoprotein and plasma oxidizability was assessed by the loss of c holesteryl esters and alpha-TOH and the accumulation of hydroperoxides of cholesteryl esters and phospholipids. Compared to native LDL, HDL, and plasma, the in vivo and in vitro alpha-TOH-depleted counterparts were highly resistant to peroxidation initiation by all oxidants when used at mild radical flux conditions. Wherever tested, the oxidizabili ty of isolated LDL decreased proportionally with decreasing alpha-TOH content. Initiation of LDL lipid oxidation by lipoxygenase and Cu2+ (e ven up to Cu2+:LDL ratio of 20:1) had an absolute requirement for alph a-TOH. Oxidation of reconstituted plasma with ROO . showed that in the absence of the vitamin, plasma lipids were largely resistant to oxida tion, whereas bilirubin and urate oxidized more rapidly. Replenishing the in vitro depleted LDL with alpha-TOH, but not with alpha-tocophero l acetate, fully restored its original content of vitamin E and its ox idizability. Similarly, dietary supplementation with alpha-TOH restore d the vitamin content and oxidizability of the in vivo alpha-TOH-deple ted lipoproteins and plasma obtained from a patient with familial isol ated vitamin E deficiency. Under high fluxes of ROO . and . OH, the ac tivity of alpha-TOH in LDL switched from pro- to anti-oxidant, with th e switching point for OH observed at a lower radical flux than that fo r ROO .. Together, our results show that alpha-TOH generally makes lip oproteins more reactive towards radical oxidants; this can result in a pro-oxidant activity depending on the specific oxidation conditions. Copyright (C) 1996 Elsevier Science Inc.