Conjugated linoleic acid is a preferential substrate for fatty acid nitration

Gustavo Bonacci, Paul R.S. Baker, Sonia R. Salvatore, Darla Shores, Nicholas K.H. Khoo, Jeffrey R. Koenitzer, Dario A. Vitturi, Steven R. Woodcock, Franca Golin-Bisello, Marsha P. Cole, Simon Watkins, Claudette St. Croix, Carlos I. Batthyany, Bruce A. Freeman, Francisco J. Schopfer

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)44071-44082
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number53
DOIs
StatePublished - Dec 28 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Bonacci, G., Baker, P. R. S., Salvatore, S. R., Shores, D., Khoo, N. K. H., Koenitzer, J. R., Vitturi, D. A., Woodcock, S. R., Golin-Bisello, F., Cole, M. P., Watkins, S., St. Croix, C., Batthyany, C. I., Freeman, B. A., & Schopfer, F. J. (2012). Conjugated linoleic acid is a preferential substrate for fatty acid nitration. Journal of Biological Chemistry, 287(53), 44071-44082. https://doi.org/10.1074/jbc.M112.401356