Studies on peroxynitrite-modified H1 histone: implications in systemic lupus erythematosus.

摘要: Peroxynitrite is a powerful nitrating and oxidizing molecule capable of modifying proteins' structure. Hyper-nitration tyrosine residues has been seen in various pathological states, including autoimmune disorders like systemic lupus erythematosus (SLE) rheumatoid arthritis. SLE, chronic disease, primarily characterized by increased levels autoantibodies, predominantly against ds-DNA. However, the initial antigenic stimulus for disease etiopathogenesis remained elusive. Carbonyl nitrotyrosine have extensively used as biomarker oxidative nitrosative stress. In this study, commercially available H1 histone was exposed to increasing concentrations peroxynitrite 30 min. The peroxynitrite-mediated structural changes were studied ultraviolet & fluorescence spectroscopy, CD, HPLC, 1-anilinonaphthalene-8-sulfonic acid binding polyacrylamide gel electrophoresis. Analysis results revealed that carbonyl contents significantly peroxynitrite-modified compared native H1. experimental animal, induced high titre antibodies H1, immunogenicity found be directly proportional content. Further, showed specificity immunogen appreciable cross-reactions with rich nitrated proteins. Formation molecular weight immune complex retarded mobility further supports anti-peroxynitrite-modified immunogen. Binding SLE anti-DNA autoantibodies analyzed direct competition ELISA. data show preferential DNA. point towards possible role etiopathogenesis.