期刊
BIOCHEMICAL JOURNAL
卷 346, 期 -, 页码 491-499出版社
PORTLAND PRESS
DOI: 10.1042/0264-6021:3460491
关键词
antioxidant; apolipoprotein B-100; ascorbate; atherosclerosis; oxidized LDL
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 mu M) with LDL resulted in concentration-dependent protection against HOCl (25-200 mu M)-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 mu M). Further, we found that HOCl (25-200 mu M)dependent formation of chloramines on apolipoprotein B-100 was fully reversed by 200 mu M 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.
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