title: 3-Nitrotyrosine: A biomarker of nitrogen free radical species modified proteins in systemic autoimmunogenic conditions.
abstract: 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 (O2(·-)) and NO, which are converted to peroxynitrite ONO2(-). 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.
authors.affiliation: Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India. Electronic address: drhahsan@gmail.com.
authors.forename: Haseeb
authors.initials: H
authors.lastname: Ahsan
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D009584:Nitrogen
keywords: 3-NT; 3-nitrotyrosine; NO; OA; RA; RNS; SLE; nitric oxide; osteoarthritis; reactive nitrogen species; rheumatoid arthritis; superoxide anion; systemic lupus erythematosus