title: Anti-inflammatory signaling actions of electrophilic nitro-arachidonic acid in vascular cells and astrocytes.
abstract: 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 nucleophilic amino acids in transcriptional regulatory proteins. Arachidonic acid (AA) represents a precursor of potent signaling molecules, i.e., prostaglandins and thromboxanes through enzymatic and non-enzymatic oxidative pathways. Arachidonic acid can be nitrated by reactive nitrogen species leading to the formation of nitro-arachidonic acid (NO2-AA). A critical issue is the influence of NO2-AA on prostaglandin endoperoxide H synthases, modulating inflammatory processes through redirection of AA metabolism and signaling. In this prospective article, we describe the key chemical and biochemical actions of NO2-AA in vascular and astrocytes. This includes the ability of NO2-AA to mediate unique redox signaling anti-inflammatory actions along with its therapeutic potential.
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Avda. General Flores 2125, Universidad de la República, Montevideo 11800, Uruguay.
authors.forename: Andrés
authors.initials: A
authors.lastname: Trostchansky
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Avda. General Flores 2125, Universidad de la República, Montevideo 11800, Uruguay. Electronic address: hrubbo@fmed.edu.uy.
authors.forename: Homero
authors.initials: H
authors.lastname: Rubbo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D016718:Arachidonic Acid / Q000737:chemistry*; D001253:Astrocytes / Q000166:cytology*; D001792:Blood Platelets / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D008055:Lipids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016718:Arachidonic Acid
keywords: Electrophilic signaling; Inflammation; Lipid nitration; Macrophages; Nitro-arachidonic acid; Platelets