Reactivity of peroxynitrite and nitric oxide with LDL.
Low density lipoprotein (LDL) oxidation by peroxynitrite is a complex process, finely modulated by control of peroxynitrite formation, LDL availability and free-radical scavenging by nitric oxide (*NO), ascorbate and alpha-tocopherol (alpha -TOH). In the presence of CO2, lipid targets are spared at the expense of surface constituents. Since surface damage may lead to oxidation-induced LDL aggregation and particle recognition by scavenger receptors, CO2 cannot be considered an inhibitor of peroxynitrite-dependent LDL modifications. Chromanols, urate and ascorbate cannot scavenge peroxynitrite in the vasculature, although intermediates of urate oxidation and high ascorbate concentrations may do soin vitro. Most if not all of the protection against peroxynitrite-induced LDL oxidation afforded by urate, ascorbate, chromanols and also*NO should be considered to depend on their free radical scavenging abilities, including inactivation of lipid peroxyl radicals (LOO),*NO2, and CO3*-; as well as their capacity to reduce high oxidation states of metal centers. Peroxynitrite direct interception by reduced manganese (II) porphyrins is possibly the most powerful although unspecific strategy to inhibit peroxynitrite reactions. In light of the recent demonstration of nitrated bioactive lipids in vivo, renewed interest in the mechanisms of peroxynitrite- and nitric oxide-mediated lipid nitration and nitrosation is guaranteed.
Botti
Horacio
H
Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Trostchansky
Andrés
A
Batthyány
Carlos
C
Rubbo
Homero
H
D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000737:chemistry / Q000502:physiology*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D024502:alpha-Tocopherol / Q000737:chemistry
D005231:Fatty Acids, Unsaturated; D008077:Lipoproteins, LDL; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D024502:alpha-Tocopherol