Peroxynitrite-modified histone as a pathophysiological biomarker in autoimmune diseases

Abstract

Under physiological conditions, reactive nitrogen and oxygen species are produced continuously. However, excess of these radicals may damage biomolecules like lipids, proteins and nucleic acids. These reactive species have been implicated in many disease conditions including acute/chronic inflammation, rheumatoid arthritis (RA), neurodegenerative diseases and systemic lupus erythematosus (SLE). Peroxynitrite, an oxidant and nitrating molecule, formed in in vivo, when nitric oxide reacts with superoxide radical. The abnormal levels of nitrotyrosine detected in tissues affected by autoimmune diseases have been attributed to peroxynitrite-mediated enhanced nitration of tyrosine residues in proteins. The chromosomal histone proteins are conserved and weak immunogens. However, they exhibit strong immunogenicity after nitration. Rabbits challenged with peroxynitrite-modified histone induce high titre antibodies, indicating that peroxynitrite modification generated immunogenic epitopes. The preferential binding of peroxynitrite-modified histones by autoantibodies derived from SLE and RA sera shows oxidatively and nitrated modified histones involve in the initiation and progression of autoimmune diseases. This review article presents the literature review of the physicochemical and immunological studies on histone proteins modified with peroxynitrite with an objective of the possible role of oxidatively nitrated histones in the initiation/progression of autoimmune inflammatory diseases.

Keywords: 3- Nitrotyrosine; Autoimmune diseases; Autoimmunity; Histones; Peroxynitrite.