title: Conjugated linoleic acid is a preferential substrate for fatty acid nitration.
abstract: The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the primary endogenous substrate for fatty acid nitration in vitro and in vivo, yielding up to 10(5) greater extent of nitration products as compared with bis-allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification. Nitroalkene derivatives of CLA and their metabolites are detected in the plasma of healthy humans and are increased in tissues undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite supplementation in rodents elevates NO(2)-CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic epithelium. These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Bonacci
authors.forename: Paul R S
authors.initials: PR
authors.lastname: Baker
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Salvatore
authors.forename: Darla
authors.initials: D
authors.lastname: Shores
authors.forename: Nicholas K H
authors.initials: NK
authors.lastname: Khoo
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Koenitzer
authors.forename: Dario A
authors.initials: DA
authors.lastname: Vitturi
authors.forename: Steven R
authors.initials: SR
authors.lastname: Woodcock
authors.forename: Franca
authors.initials: F
authors.lastname: Golin-Bisello
authors.forename: Marsha P
authors.initials: MP
authors.lastname: Cole
authors.forename: Simon
authors.initials: S
authors.lastname: Watkins
authors.forename: Claudette
authors.initials: C
authors.lastname: St Croix
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Batthyany
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
mesh_terms: D000818:Animals; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019787:Linoleic Acid