CELLULAR THIOL PRODUCTION AND OXIDATION OF LOW-DENSITY-LIPOPROTEIN

Compelling evidence suggests that low-density lipoprotein (LDL) is oxi dized by cells within the arterial intima and that, once oxidized, it is profoundly atherogenic. The precise mechanism(s) by which cells pro mote the oxidation of LDL in vivo are not known; in vitro, however, ox idation of LDL can be enhanced by a number of differing mechanisms, in cluding reaction with free and protein-bound metal ions, thiols, react ive oxygen species, lipoxygenase, myeloperoxidase and peroxynitrite. T his 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 metal s.