Campolo Nicolás, Bartesaghi Silvina, Radi Rafael
Redox Rep. 2014 Nov;19(6):221-31. doi: 10.1179/1351000214Y.0000000099. Epub 2014 Jun 30.
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.
蛋白质酪氨酸硝化是一种氧化后修饰，可影响蛋白质的结构和功能。它在体内由一氧化氮衍生的活性氮物质（RNS）介导产生，包括过氧亚硝酸根（ONOO(-)）和二氧化氮（(•)NO₂）。氧化还原活性过渡金属，如铁（Fe）、铜（Cu）和锰（Mn），可积极参与生物系统中酪氨酸硝化过程，因为它们催化活性氧和RNS的产生，提高硝化产率并为该过程提供位点特异性。在发现蛋白质酪氨酸硝化可在生物学相关条件下发生后不久，就表明一些低分子量过渡金属中心和金属蛋白可促进过氧亚硝酸根依赖性硝化。后来的研究表明，硝化也可通过不依赖过氧亚硝酸根的途径实现，这取决于过渡金属在过氧化氢存在下催化亚硝酸盐（NO₂(-)）氧化为(•)NO₂。这些过程可通过血红素过氧化物酶依赖性反应或通过亚铁离子和亚铜离子通过芬顿型化学实现。除了体外证据外，现在有几项体内研究支持过渡金属水平与蛋白质酪氨酸硝化之间的密切关系。因此，过渡金属对在基础条件下观察到的酪氨酸硝化蛋白质水平的贡献，特别是在与这些金属离子高水平相关的疾病状态下的贡献，似乎相当明显。总之，目前的证据明确支持过渡金属在确定由过氧亚硝酸根依赖性和非依赖性机制介导的蛋白质酪氨酸硝化的程度和选择性方面的核心作用。
