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Annu Rev Physiol. 2014;76:79-105. doi: 10.1146/annurev-physiol-021113-170341. Epub 2013 Oct 16.

Redox-dependent anti-inflammatory signaling actions of unsaturated fatty acids.

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1
Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; email: mmd33@pitt.edu , freerad@pitt.edu , gstacy@pitt.edu.

Abstract

Unsaturated fatty acids are metabolized to reactive products that can act as pro- or anti-inflammatory signaling mediators. Electrophilic fatty acid species, including nitro- and oxo-containing fatty acids, display salutary anti-inflammatory and metabolic actions. Electrophilicity can be conferred by both enzymatic and oxidative reactions, via the homolytic addition of nitrogen dioxide to a double bond or via the formation of α,β-unsaturated carbonyl and epoxide substituents. The endogenous formation of electrophilic fatty acids is significant and influenced by diet, metabolic, and inflammatory reactions. Transcriptional regulatory proteins and enzymes can sense the redox status of the surrounding environment upon electrophilic fatty acid adduction of functionally significant, nucleophilic cysteines. Through this covalent and often reversible posttranslational modification, gene expression and metabolic responses are induced. At low concentrations, the pleiotropic signaling actions that are regulated by these protein targets suggest that some classes of electrophilic lipids may be useful for treating metabolic and inflammatory diseases.

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