US EPA

1485398 

Journal Article 

Conjugated linoleic acid is a preferential substrate for fatty acid nitration 

Bonacci, G; Baker, PR; Salvatore, , SR; Shores, D; Khoo, NK; Koenitzer, , JR; Vitturi, DA; Woodcock, , SR; Golin-Bisello, F; Cole, MP; Watkins, S; St Croix, C; Batthyany, CI; Freeman, BA; Schopfer, FJ 

2012 

Yes 

Journal of Biological Chemistry
ISSN: 0021-9258
EISSN: 1083-351X 

287 

53 

44071-44082 

English 

23144452 

10.1074/jbc.M112.401356 

WOS:000312938600006 

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.