Protein Targets and Functional Consequences of Tyrosine Nitration in Vascular Disease

Redox Proteomics: Chemical Principles, Methodological Approaches and Biological/Biomedical Promises

“…A variety of reactive species and multiple reaction pathways concur to modify tyrosine in vivo yielding NO 2 -Tyr, whose presence is generally the result of a combined, simultaneous production of various RNS (Figure A). Most pathways involve a free radical biochemistry with carbonate radicals (CO 3 • ) and/or oxo-metal complexes that oxidize tyrosine to a tyrosyl radical (Tyr • ), followed by a very rapid, diffusion-controlled reaction with NO 2 • yielding NO 2 -Tyr.…”

“…Selectivity of protein tyrosine nitration is due to different parameters, which include (i) cellular localization of the target protein and its proximity to the generation of nitration agents, (ii) local electrostatic environment sorrounding the target tyrosine residue, (iii) relative tyrosine accessibility on protein surface, and (iv) absence of steric hindrance factors. , Conversely, protein abundance, total number of tyrosine residues, and primary sequence are not dominant factors in tyrosine nitration selectivity. , Thus, nitration of protein tyrosine residues represents a dynamic and selective process, rather than a random, indiscriminate event; this conclusion is supported by numerous studies on pathological conditions associated with oxidative stress, where this modification is limited to certain cell types and to selective sites of injury …”

“…In this context, elevated NO 2 -Tyr levels have been observed for acute and chronic disease states (i.e., during vascular diseases) generally associated with oxidative stress. In this case, specific nitrated proteins have been demonstrated, whose functional changes (usually in a negative manner) may reflect disease progression. ,, For example, actin nitration has been shown to reduce the dynamic assembly/disassembly process of protein filaments in the vasculature, kidney, and liver of patients affected with sickle cell disease. In addition to adversely affecting vascular function, selective nitration of tissutal actin tyrosine may lead to cell apoptotis and loss of organ function observed in this pathology .…”

Corneal Protein Nitration in Experimental Uveitis

“…NO 2 ) (16). Myeloperoxidase (MPO), a heme peroxidase released during neutrophil, monocyte, and macrophage activation, can give rise to nitrotyrosine formation (11). As stated previously, LPS-induced changes in corneal cell ultrastructure initiate an inflammatory response which is causally linked to activation and adherence of neutrophils.…”

“…The oxidation and nitration of lipids, amino acids, and proteins will alter biomolecular structure and function and at the same time reveal the pathogenic actions of reactive species (11). Corneal protein nitration has been observed in human corneal diseases such as keratoconus, Fuchs endothelial dystrophy, and in stored human corneal epithelium (12).…”