title: Vitamin C protects against and reverses specific hypochlorous acid- and chloramine-dependent modifications of low-density lipoprotein.
abstract: Activated phagocytes produce the highly reactive oxidant hypochlorous acid (HOCl) via the myeloperoxidase-catalysed reaction of hydrogen peroxide with chloride ions. HOCl reacts readily with a number of susceptible targets on apolipoprotein B-100 of low-density lipoprotein (LDL), resulting in uncontrolled uptake of HOCl-modified LDL by macrophages. We have investigated the effects of vitamin C (ascorbate), an effective water-soluble antioxidant, on the HOCl- and chloramine-dependent modification of LDL. Co-incubation of vitamin C (25-200 microM) with LDL resulted in concentration-dependent protection against HOCl (25-200 microM)-mediated oxidation of tryptophan and lysine residues, formation of chloramines and increases in the relative electrophoretic mobility of LDL. Vitamin C also partially protected against oxidation of cysteine residues by HOCl, and fully protected against oxidation of these residues by the low-molecular-mass chloramines, N(alpha)-acetyl-lysine chloramine and taurine chloramine, and to a lesser extent monochloramine (each at 25-200 microM). Further, we found that HOCl (25-200 microM)-dependent formation of chloramines on apolipoprotein B-100 was fully reversed by 200 microM vitamin C; however, the loss of lysine residues and increase in relative electrophoretic mobility of LDL were only partially reversed, and the loss of tryptophan and cysteine residues was not reversed. Time-course experiments showed that the reversal by vitamin C of HOCl-dependent modifications became less efficient as the LDL was incubated for up to 4 h at 37 degrees C. These data show that vitamin C not only protects against, but also reverses, specific HOCl- and chloramine-dependent modifications of LDL. As HOCl-mediated LDL modifications have been strongly implicated in the pathogenesis of atherosclerosis, our data indicate that vitamin C could contribute to the anti-atherogenic defence against HOCl.
authors.affiliation: Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331, USA. anitra.carr@orst.edu
authors.forename: A C
authors.initials: AC
authors.lastname: Carr
authors.forename: T
authors.initials: T
authors.lastname: Tijerina
authors.forename: B
authors.initials: B
authors.lastname: Frei
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism*; D002700:Chloramines / Q000378:metabolism; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male
chemical_list: D002700:Chloramines; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006997:Hypochlorous Acid; C030816:chloramine; D001205:Ascorbic Acid