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Hum Immunol. 2013 Oct;74(10):1392-9. doi: 10.1016/j.humimm.2013.06.009. Epub 2013 Jun 15.

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

Author information

1
Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India. Electronic address: drhahsan@gmail.com.

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.

KEYWORDS:

3-NT; 3-nitrotyrosine; NO; OA; RA; RNS; SLE; nitric oxide; osteoarthritis; reactive nitrogen species; rheumatoid arthritis; superoxide anion; systemic lupus erythematosus

PMID:
23777924
DOI:
10.1016/j.humimm.2013.06.009
[Indexed for MEDLINE]

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