title: Redox signaling in inflammation: interactions of endogenous electrophiles and mitochondria in cardiovascular disease.
abstract: Reactive species derived from oxygen and nitric oxide are produced during inflammation and promote oxidation and nitration of biomolecules, including unsaturated fatty acids. Among the products of these reactions are alpha,beta-unsaturated carbonyl and nitro derivatives of fatty acids, electrophilic species whose reactivity with nucleophilic amino acids provides a means of posttranslational protein modification and signaling. These electrophilic fatty acids activate cytosolic and nuclear stress-response pathways (through Nrf2/Keap1 and PPARgamma, for example). There is also growing evidence that mitochondria generate electrophilic species. This appreciation, when combined with the role of mitochondrial dysfunction in conditions where exogenously delivered electrophiles exhibit therapeutic benefit, suggests that mitochondrial electrophile targets are also important in the resolution and prevention of inflammatory injury. Cardioprotective signaling pathways in particular appear to converge on mitochondria, with nitro-fatty acids recently shown to protect against cardiac ischemia/reperfusion injury in a murine model. Although numerous mitochondrial proteins are subject to modification by electrophiles, defining the targets most relevant to cytoprotection during inflammatory stress remains a clinically relevant goal.
authors: Dept. of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
authors: Jeffrey R
authors: JR
authors: Koenitzer
authors: Bruce A
authors: BA
authors: Freeman
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005227:Fatty Acids