Faculty Collaboration Database

Protein tyrosine nitration in hydrophilic and hydrophobic environments. Amino Acids 2007;32(4):501-15

Date

11/02/2006

Pubmed ID

17077966

DOI

10.1007/s00726-006-0425-8

Scopus ID

2-s2.0-34249101633 (requires institutional sign-in at Scopus site)   122 Citations

Abstract

In this review we address current concepts on the biological occurrence, levels and consequences of protein tyrosine nitration in biological systems. We focused on mechanistic aspects, emphasizing on the free radical mechanisms of protein 3-nitrotyrosine formation and critically analyzed the restrictions for obtaining large tyrosine nitration yields in vivo, mainly due to the presence of strong reducing systems (e.g. glutathione) that can potently inhibit at different levels the nitration process. Evidence is provided to show that the existence of metal-catalyzed processes, the assistance of nitric oxide-dependent nitration steps and the facilitation by hydrophobic environments, provide individually and/or in combination, feasible scenarios for nitration in complex biological milieux. Recent studies using hydrophobic tyrosine analogs and tyrosine-containing peptides have revealed that factors controlling nitration in hydrophobic environments such as biomembranes and lipoproteins can differ to those in aqueous compartments. In particular, exclusion of key soluble reductants from the lipid phase will more easily allow nitration and lipid-derived radicals are suggested as important mediators of the one-electron oxidation of tyrosine to tyrosyl radical in proteins associated to hydrophobic environments. Development and testing of hydrophilic and hydrophobic probes that can compete with endogenous constituents for the nitrating intermediates provide tools to unravel nitration mechanisms in vitro and in vivo; additionally, they could also serve to play cellular and tissue protective functions against the toxic effects of protein tyrosine nitration.

Author List

Bartesaghi S, Ferrer-Sueta G, Peluffo G, Valez V, Zhang H, Kalyanaraman B, Radi R

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Membrane
Dimerization
Free Radicals
Hydrophobic and Hydrophilic Interactions
Peptides
Proteins
Tyrosine