Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

摘要

Unsaturated fatty acids are metabolized to reactive products that can act as pro- or anti-inflammatory signaling mediators. Electrophilic fatty acid species, incl tiding nitro- and oxo-containing fatty acids, display salutary anti-inflammatory and metabolic actions. Elcctrophilicity can be conferred by both enzymatic and oxi dative reactions, via the homolytic addition of nitrogen dioxide to a double bond or via the formation of alpha, beta-unsaturated car-bonyl and cpoxide suhstituents. The endogenous formation of electrophilic fatty acids is significant and influenced by diet, metabolic, and inflammatory reactions. Transcriptional regulator)' 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.