Monocyte superoxide production is inversely related to normal content of alpha-tocopherol in low-density lipoprotein.
Vitamin E (alpha-tocopherol) is a potent peroxyl radical scavenger. According to the oxidative theory of atherosclerosis, it prevents oxidation of low-density lipoprotein (LDL) and thereby lowers the risk of cardiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O2.--production), which is involved in LDL oxidation. We investigated whether alpha-tocopherol-containing LDL decreases this production in a manner dependent on the LDL alpha-tocopherol content (the alpha-tocopherol/apoB molar ratio) in human, phorbol ester-stimulated, adherent monocytes. We found that O2.--production was inhibited by native LDL (n-LDL) in a manner highly sensitive to the increasing alpha-tocopherol content (range 4.5 8). In addition: (1) inhibition was greater when alpha-tocopherol was associated to acetylated LDL (ac-LDL), the maximal percentage of inhibition being 80% as opposed to 35% for n-LDL; (2) the alpha-tocopherol overloading of either form of LDL did not produce further inhibition; (3) the free form of alpha-tocopherol produced lower inhibition compared with the lipoprotein-associated forms; (4) inhibition was not related to the cell content of alpha-tocopherol. We propose that the cell targeting of alpha-tocopherol is crucial to the inhibition of monocyte O2.--production, and thus that the role of normal LDL-alpha-tocopherol contents (range 6-8) in the prevention of atherogenic processes needs to be reexamined.
Laboratoire de Biologie et Biochimie des Lipides, EA 2033, Institut de Biologie, Faculté de Médecine, Université de Montpellier, France.
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D001161:Arteriosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism*; D014810:Vitamin E / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D013481:Superoxides; D014810:Vitamin E