3-Nitrotyrosine: A biomarker of nitrogen free radical species modified proteins in systemic autoimmunogenic conditions

The free radical-mediated damage to proteins results in the modification of amino acid residues, cross-linking of side chains and fragmentation. L-Tyrosine and protein bound tyrosine are prone to attack by various mediators and reactive nitrogen intermediates to form 3-nitrotyrosine (3-NT). Activated macrophages produce superoxide (O-2(-) and NO, which are converted to peroxynitrite ONO. 3-NT formation is also catalyzed by a class of peroxidases utilizing nitrite and hydrogen peroxide as substrates. Evidence supports the formation of 3-NT in vivo in diverse pathologic conditions and 3-NT is thought to be a relatively specific marker of oxidative damage mediated by peroxynitrite. Free/protein-bound tyrosines are attacked by various RNS, including peroxynitrite, to form free/protein-bound 3-NT, which may provide insight into the etiopathogenesis of autoimmune conditions. The formation of nitrotyrosine represents a specific peroxynitrite-mediated protein modification; thus, detection of nitrotyrosine in proteins is considered as a biomarker for endogenous peroxynitrite activity. The peroxynitrite-driven oxidation and nitration of biomolecules may lead to autoimmune diseases such as systemic lupus. The subsequent release of altered proteins may enable them to act as antigen-inducing antibodies against self-proteins. Hence, tyrosine nitrated proteins can act as neoantigens and lead to the generation of autoantibodies against self proteins in various autoimmune disorders. (C) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.