Cellular thiol production and oxidation of low-density lipoprotein.
Compelling evidence suggests that low-density lipoprotein (LDL) is oxidized by cells within the arterial intima and that, once oxidized, it is profoundly atherogenic. The precise mechanism(s) by which cells promote the oxidation of LDL in vivo are not known; in vitro, however, oxidation of LDL can be enhanced by a number of differing mechanisms, including reaction with free and protein-bound metal ions, thiols, reactive oxygen species, lipoxygenase, myeloperoxidase and peroxynitrite. This review is concerned with the mechanisms by which cells enhance the oxidation of LDL in the presence of transition metals; in particular, the regulation, pro- and anti-oxidant consequences, and mechanism of action of cellular thiol production are examined, and contrasted with thiol-independent oxidation of LDL in the presence of transition metals.
Graham
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Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, London, UK. agraham@rfhsm.ac.uk
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003553:Cystine / Q000378:metabolism / Q000493:pharmacokinetics; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D008074:Lipoproteins; D008670:Metals; D013438:Sulfhydryl Compounds; D013481:Superoxides; D003553:Cystine; D003300:Copper; D007501:Iron