The nitric oxide congener nitrite inhibits myeloperoxidase/H2O2/ Cl- -mediated modification of low density lipoprotein.
Nitric oxide, a pivotal molecule in vascular homeostasis, is converted under aerobic conditions to nitrite. Recent studies have shown that myeloperoxidase (MPO), an abundant heme protein released by activated leukocytes, can oxidize nitrite (NO(2-)) to a radical species, most likely nitrogen dioxide. Furthermore, hypochlorous acid (HOCl), the major strong oxidant generated by MPO in the presence of physiological concentrations of chloride ions, can also react with nitrite, forming the reactive intermediate nitryl chloride. Since MPO and MPO-derived HOCl, as well as reactive nitrogen species, have been implicated in the pathogenesis of atherosclerosis through oxidative modification of low density lipoprotein (LDL), we investigated the effects of physiological concentrations of nitrite (12.5-200 microm) on MPO-mediated modification of LDL in the absence and presence of physiological chloride concentrations. Interestingly, nitrite concentrations as low as 12.5 and 25 microm significantly decreased MPO/H2O2)/Cl- -induced modification of apoB lysine residues, formation of N-chloramines, and increases in the relative electrophoretic mobility of LDL. In contrast, none of these markers of LDL atherogenic modification were affected by the MPO/H2O2/NO2-) system. Furthermore, experiments using ascorbate (12.5-200 microm) and the tyrosine analogue 4-hydroxyphenylacetic acid (12.5-200 microm), which are both substrates of MPO, indicated that nitrite inhibits MPO-mediated LDL modifications by trapping the enzyme in its inactive compound II form. These data offer a novel mechanism for a potential antiatherogenic effect of the nitric oxide congener nitrite.
Carr
A C
AC
Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA. anitra.carr@orst.edu
Frei
B
B
D002712:Chlorides / Q000037:antagonists & inhibitors*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism*; D009195:Peroxidase / Q000037:antagonists & inhibitors*
D002712:Chlorides; D008077:Lipoproteins, LDL; D009573:Nitrites; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase