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Antioxid Redox Signal. 2013 Oct 10;19(11):1257-65. doi: 10.1089/ars.2012.5023. Epub 2012 Dec 20.

Nitro-fatty acids: formation, redox signaling, and therapeutic potential.

Author information

  • 1Department of Biochemistry, Faculty of Medicine and Center for Free Radical and Biomedical Research, University of the Republic, Montevideo, Uruguay .

Abstract

SIGNIFICANCE:

Nitrated derivatives of unsaturated fatty acids (nitro-fatty acids) are being formed and detected in human plasma, cell membranes, and tissue, triggering signaling cascades via covalent and reversible post-translational modifications of susceptible nucleophilic amino acids in transcriptional regulatory proteins and enzymes.

RECENT ADVANCES:

Nitro-fatty acids modulate metabolic as well as inflammatory signaling pathways, including the p65 subunit of nuclear factor κB and the transcription factor peroxisome proliferator-activated receptor-γ. Moreover, nitro-fatty acids can activate heat shock as well as phase II antioxidant responses. As electrophiles, they also activate the Nuclear factor erythroid 2-related factor 2 pathway.

CRITICAL ISSUES:

We first discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties, including their capacity to release nitric oxide and exert antioxidant actions. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, modulating inflammatory processes through redirection of arachidonic acid metabolism and signaling.

FUTURE DIRECTIONS:

Based on this information, we analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases associated with oxidative and nitrative stress conditions. A key future issue is to evaluate whether nitro-fatty acid supplementation would be useful for human diseases linked to inflammation as well as their potential toxicity when administered by long periods of time.

PMID:
23256873
[PubMed - indexed for MEDLINE]
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