Nitrogen dioxide radical generated by the myeloperoxidase-hydrogen peroxide-nitrite system promotes lipid peroxidation of low density lipoprotein.
Myeloperoxidase, a heme protein secreted by activated phagocytes, is present and enzymatically active in human atherosclerotic lesions. In the current studies, we explored the possibility that reactive nitrogen species generated by myeloperoxidase promote lipid peroxidation of low density lipoprotein (LDL) -- a modification that may render the lipoprotein atherogenic. We found that myeloperoxidase, an H2O2-generating system and nitrite (NO2-) peroxidized LDL lipids. The process required NO2- and each component of the enzymatic system; it was inhibited by catalase, cyanide and ascorbate, a potent scavenger of aqueous phase radicals. LDL peroxidation did not require chloride ion, and it was little affected by the hypochlorous acid scavenger taurine. Collectively, these results suggest that lipid peroxidation is promoted by a nitrogen dioxide radical-like species. These observations indicate that myeloperoxidase, by virtue of its ability to form reactive nitrogen intermediates, may promote lipid peroxidation and atherogenesis.
Byun
J
J
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mueller
D M
DM
Fabjan
J S
JS
Heinecke
J W
JW
D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology; D001205:Ascorbic Acid / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D008077:Lipoproteins, LDL; D009573:Nitrites; D014810:Vitamin E; D006861:Hydrogen Peroxide; D009195:Peroxidase; D011341:Probucol; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide