title: Metal-catalyzed protein tyrosine nitration in biological systems.
abstract: Protein tyrosine nitration is an oxidative postranslational modification that can affect protein structure and function. It is mediated in vivo by the production of nitric oxide-derived reactive nitrogen species (RNS), including peroxynitrite (ONOO(-)) and nitrogen dioxide ((•)NO₂). Redox-active transition metals such as iron (Fe), copper (Cu), and manganese (Mn) can actively participate in the processes of tyrosine nitration in biological systems, as they catalyze the production of both reactive oxygen species and RNS, enhance nitration yields and provide site-specificity to this process. Early after the discovery that protein tyrosine nitration can occur under biologically relevant conditions, it was shown that some low molecular weight transition-metal centers and metalloproteins could promote peroxynitrite-dependent nitration. Later studies showed that nitration could be achieved by peroxynitrite-independent routes as well, depending on the transition metal-catalyzed oxidation of nitrite (NO₂(-)) to (•)NO₂ in the presence of hydrogen peroxide. Processes like these can be achieved either by hemeperoxidase-dependent reactions or by ferrous and cuprous ions through Fenton-type chemistry. Besides the in vitro evidence, there are now several in vivo studies that support the close relationship between transition metal levels and protein tyrosine nitration. So, the contribution of transition metals to the levels of tyrosine nitrated proteins observed under basal conditions and, specially, in disease states related with high levels of these metal ions, seems to be quite clear. Altogether, current evidence unambiguously supports a central role of transition metals in determining the extent and selectivity of protein tyrosine nitration mediated both by peroxynitrite-dependent and independent mechanisms.
authors: Nicolás
authors: N
authors: Campolo
authors: Silvina
authors: S
authors: Bartesaghi
authors: Rafael
authors: R
authors: Radi
mesh_terms: D000818:Animals; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007477:Ions; D008670:Metals / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry; D009573:Nitrites / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D026361:Reactive Nitrogen Species / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D007477:Ions; D008670:Metals; D009573:Nitrites; D011506:Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D014443:Tyrosine; D006861:Hydrogen Peroxide; D009584:Nitrogen
keywords: Free radicals; Hydrogen peroxide; Nitration; Nitric oxide; Nitrogen dioxide; Oxidative stress; Superoxide; Transition metals