title: Nitro-fatty acids: formation, redox signaling, and therapeutic potential.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Center for Free Radical and Biomedical Research, University of the Republic, Montevideo, Uruguay .
authors.forename: Andrés
authors.initials: A
authors.lastname: Trostchansky
authors.forename: Lucía
authors.initials: L
authors.lastname: Bonilla
authors.forename: Lucía
authors.initials: L
authors.lastname: González-Perilli
authors.forename: Homero
authors.initials: H
authors.lastname: Rubbo
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D008074:Lipoproteins; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases