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Immunopharmacol Immunotoxicol. 2009;31(3):388-96. doi: 10.1080/08923970802709197.

Biochemical and cellular toxicology of peroxynitrite: implications in cell death and autoimmune phenomenon.

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  • 1Department of Biochemistry, Sardar Bhagwan Singh Post-Graduate Institute of Biomedical Sciences and Research, Balawala, Dehradun 248161, India.

Abstract

Reactive nitrogen species include nitric oxide (.NO), peroxynitrite (ONOO(-)) and nitrogen dioxide radical (NO2*). Peroxynitrite is a reactive oxidant, produced from nitric oxide (*NO) and superoxide anion (O(2*-), that reacts with a variety of biological macromolecules. It is produced in the body in response to physiological stress and environmental toxins. It is a potent trigger of oxidative protein and DNA damage-including DNA strand breakage and base modification. It activates the nuclear enzyme poly-ADP ribose polymerase (PARP) resulting in energy depletion and apoptosis/necrosis of cells. Peroxynitrite generation is a crucial pathological mechanism in stroke, diabetes, inflammation, neurodegeneration, cancer, etc. Peroxynitrite modified DNA may also lead to the generation of autoantibodies in various autoimmune disorders such as systemic lupus erythematosus (SLE). In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA, generating neoepitopes leading to the production of autoantibodies. Hence, understanding the pathophysiology of peroxynitrite could lead to important therapeutic interventions.

PMID:
19555204
[PubMed - indexed for MEDLINE]
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