Peroxynitrite - An ugly biofactor ?

Cellular damage occurring under oxidative conditions has been ascribed mainly to the formation of peroxynitrite (ONOOH/ONOO-) that originates from the reaction of NO• with O2•-. The detrimental effects of peroxynitrite are exacerbated by the reaction with CO2 that leads to ONOOC(O)O-, which further decays to the strong oxidant radicals NO2• and CO3•-. The reaction with CO2, however, may redirect peroxynitrite specificity. An excessive formation of peroxynitrite represents an important mechanism contributing to the DNA damage, the inactivation of metabolic enzymes, ionic pumps, and structural proteins, and the disruption of cell membranes. Because of its ability to oxidize biomolecules, peroxynitrite is implicated in an increasing list of diseases, including neurodegenerative and cardiovascular disorders, inflammation, pain, autoimmunity, cancer, and aging. However, peroxynitrite displays also protective activities: (i) at high concentrations, it shows anti-viral, anti-microbial, and anti-parasitic actions; and (ii) at low concentrations, it stimulates protective mechanisms in the cardiovascular, nervous, and respiratory systems. The detrimental effects of peroxynitrite and related reactive species are impaired by (pseudo-) enzymatic systems, mainly represented by heme-proteins (e.g., hemoglobin and myoglobin). Here, we report biochemical aspects of peroxynitrite actions being at the root of its biomedical effects. Copyright