TY - JOUR
T1 - Conjugated linoleic acid is a preferential substrate for fatty acid nitration
AU - Bonacci, Gustavo
AU - Baker, Paul R.S.
AU - Salvatore, Sonia R.
AU - Shores, Darla
AU - Khoo, Nicholas K.H.
AU - Koenitzer, Jeffrey R.
AU - Vitturi, Dario A.
AU - Woodcock, Steven R.
AU - Golin-Bisello, Franca
AU - Cole, Marsha P.
AU - Watkins, Simon
AU - St. Croix, Claudette
AU - Batthyany, Carlos I.
AU - Freeman, Bruce A.
AU - Schopfer, Francisco J.
PY - 2012/12/28
Y1 - 2012/12/28
N2 - 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 105 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 NO2-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.
AB - 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 105 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 NO2-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.
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U2 - 10.1074/jbc.M112.401356
DO - 10.1074/jbc.M112.401356
M3 - Article
C2 - 23144452
AN - SCOPUS:84871724685
SN - 0021-9258
VL - 287
SP - 44071
EP - 44082
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 53
ER -