Analysis of Nitroproteome in Human Pituitary Adenomas

Protein tyrosine nitration is an important reactive oxygen species/reactive nitrogen species (ROS/RNS)-related modification that is derived from the main in vivo peroxynitrite pathway and the secondary myeloperoxidase reaction pathway (Scaloni, 2006, Khan et al., 1998, Zhan & Desiderio, 2009a, 2009b, and 2009c, Dalle-Donne et al., 2005, Zhan, Wang, & Desiderio, 2013). Tyrosine nitration adds an electron-withdrawing nitro group (–NO2) to the tyrosine phenolic ring (Zhan & Desiderio, 2006). Addition of this nitro group will decrease the electron density of the tyrosine phenolic ring, change the phenolic pKa value (from ~10 for tyrosine) into the physiological pH range (~7.1 for 3nitrotyrosine), and affect chemical properties of the tyrosine residue (Zhan & Desiderio, 2006, Yee et al., 2003, Irie et al., 2003). Thus, the decreased electron density will negatively affect the interaction intensity between enzyme-substrate, receptor-ligand, or antigenantibody when the nitration occurred within those interacting regions, and impact on functions of that protein (Zhan & Desiderio, 2006). Moreover, in vivo protein tyrosine nitration might be denitrated with a putative denitrase to result in a dynamically reversible process between nitration and denitration (Irie et al., 2003, Aulak et al., 2004, Koeck et al., 2004). Thus, protein nitration would have a biological function such as neurotransmission and redox signaling besides its pathological consequences. Tyrosine ni-