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

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


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmunity
  • Biomarkers / metabolism
  • Free Radicals / metabolism
  • Humans
  • Nitrogen / metabolism
  • Oxidation-Reduction
  • Proteins / immunology
  • Proteins / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry
  • Tyrosine / metabolism


  • Biomarkers
  • Free Radicals
  • Proteins
  • 3-nitrotyrosine
  • Tyrosine
  • Nitrogen