Khan Md Asad, Alam Khursheed, Zafaryab Md, Rizvi M Moshahid A
Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India.
Department of Biochemistry, Jawaharlal Nehru Medical College, AMU, Aligarh, 202002, India.
Biochimie. 2017 Sep;140:1-9. doi: 10.1016/j.biochi.2017.06.006. Epub 2017 Jun 12.
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.
在生理条件下，活性氮和氧物种会持续产生。然而，这些自由基过量可能会损害脂质、蛋白质和核酸等生物分子。这些活性物种与许多疾病状况有关，包括急性/慢性炎症、类风湿性关节炎（RA）、神经退行性疾病和系统性红斑狼疮（SLE）。过氧亚硝酸盐是一种氧化剂和硝化分子，在体内由一氧化氮与超氧自由基反应形成。在受自身免疫性疾病影响的组织中检测到的硝基酪氨酸异常水平，归因于过氧亚硝酸盐介导的蛋白质中酪氨酸残基硝化增强。染色体组蛋白是保守的弱免疫原。然而，它们在硝化后表现出强免疫原性。用过氧亚硝酸盐修饰的组蛋白攻击兔子会诱导产生高滴度抗体，表明过氧亚硝酸盐修饰产生了免疫原性表位。来自SLE和RA血清的自身抗体对过氧亚硝酸盐修饰的组蛋白的优先结合表明，氧化和硝化修饰的组蛋白参与了自身免疫性疾病的起始和进展。这篇综述文章介绍了用过氧亚硝酸盐修饰的组蛋白的物理化学和免疫学研究的文献综述，目的是探讨氧化硝化组蛋白在自身免疫性炎症疾病起始/进展中的可能作用。
