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Redox signaling in inflammation: interactions of endogenous electrophiles and mitochondria in cardiovascular disease
Author(s) -
Koenitzer Jeffrey R.,
Freeman Bruce A.
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05559.x
Subject(s) - electrophile , mitochondrion , chemistry , cytosol , biochemistry , nitric oxide , cytoprotection , reactive oxygen species , inflammation , nucleophile , oxidative stress , reactive nitrogen species , microbiology and biotechnology , biology , enzyme , immunology , organic chemistry , catalysis
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 α,β‐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 PPARγ, 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.