Conjugated Linoleic Acid Is a Preferential Substrate for Fatty Acid Nitration

被引：123

作者：

Bonacci, Gustavo ^{[1
]}

Baker, Paul R. S. ^{[1
]}

Salvatore, Sonia R. ^{[1
]}

Shores, Darla ^{[2
]}

Khoo, Nicholas K. H. ^{[1
]}

Koenitzer, Jeffrey R. ^{[1
]}

Vitturi, Dario A. ^{[1
]}

Woodcock, Steven R. ^{[1
]}

Golin-Bisello, Franca ^{[1
]}

Cole, Marsha P. ^{[1
]}

Watkins, Simon ^{[3
]}

Croix, Claudette St. ^{[3
]}

Batthyany, Carlos I. ^{[4
]}

Freeman, Bruce A. ^{[1
]}

Schopfer, Francisco J. ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA

[4] Inst Pasteur, Montevideo 11400, Uruguay

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2012年 / 287卷 / 53期

基金：

美国国家卫生研究院;

关键词：

NITRIC-OXIDE; NITROGEN-DIOXIDE; HUMAN BLOOD; ISCHEMIA; INFLAMMATION; NITROALKENE; GENERATION; MYELOPEROXIDASE; PEROXYNITRITE; REPERFUSION;

D O I：

10.1074/jbc.M112.401356

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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.

引用

页码：44071 / 44082

页数：12

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