Peroxynitrite—An ugly biofactor?

Abstract

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 O(2) (*-). The detrimental effects of peroxynitrite are exacerbated by the reaction with CO(2) that leads to ONOOC(O)O(-), which further decays to the strong oxidant radicals NO(2) (*) and CO(3) (*-). The reaction with CO(2), 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.

Pentoxifylline alleviates vascular impairment in insulin resistance via TNF-α inhibition

“…We previously showed that TNF-α directly impairs pulmonary artery endothelialdependent relaxation mediated by stimulation of ROS generation and NO synthase uncoupling (El-Bassossy et al 2009). The role of reactive nitrogen species (nitrosative stress) and associated pathways in the pathogenesis of cardiovascular disease has been widely accepted (Ascenzi et al 2010). TNF-α can also impair vascular contractility indirectly through stimulation of leukocytes infiltration.…”

Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation

“…Surprisingly, besides this, ONOO -exhibits significant biomedical effects -protective effect i) at high concentrations -it behaves as anti-viral, anti-microbial, and anti-parasitic agent, and ii) at low concentrations, it stimulates protective mechanisms in the cardiovascular, nervous, and respiratory systems (Ascenzi et al 2010).…”

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

“…ONOO − and its derivatives (e.g. nitrogen dioxide (·NO 2 ), dinitrogen trioxide (N 2 O 3 ) and peroxynitrous acid (ONOOH)) can easily penetrate the cellular membrane and modify proteins, lipids and DNA [13,33]. In cells, ONOO − mediates nitration of tyrosine and tryptophan residues and Snitrosylation of thiol group in proteins, which in turn modifies their functions [79,181] (Fig.…”