HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 47, 35686-35698, November 24, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/47/35686    most recent M603357200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cui, T. Articles by Chen, Y. E. Search for Related Content PubMed PubMed Citation Articles by Cui, T. Articles by Chen, Y. E. Social Bookmarking                      What's this?

Nitrated Fatty Acids: Endogenous Anti-inflammatory Signaling Mediators^*

Taixing Cui¹², Francisco J. Schopfer²³, Jifeng Zhang, Kai Chen, Tomonaga Ichikawa, Paul R. S. Baker⁴, Carlos Batthyany, Balu K. Chacko^¶3, Xu Feng^¶, Rakesh P. Patel^¶, Anupam Agarwal^||, Bruce A. Freeman⁵, and Yuqing E. Chen⁶

From the Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109, the Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, the ^¶Department of Pathology and ^||Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294

Nitroalkene derivatives of linoleic acid (LNO₂) and oleic acid (OA-NO₂) are present; however, their biological functions remain to be fully defined. Herein, we report that LNO₂ and OA-NO₂ inhibit lipopolysaccharide-induced secretion of proinflammatory cytokines in macrophages independent of nitric oxide formation, peroxisome proliferator-activated receptor- activation, or induction of heme oxygenase-1 expression. The electrophilic nature of fatty acid nitroalkene derivatives resulted in alkylation of recombinant NF-B p65 protein in vitro and a similar reaction with p65 in intact macrophages. The nitroalkylation of p65 by fatty acid nitroalkene derivatives inhibited DNA binding activity and repressed NF-B-dependent target gene expression. Moreover, nitroalkenes inhibited endothelial tumor necrosis factor--induced vascular cell adhesion molecule 1 expression and monocyte rolling and adhesion. These observations indicate that nitroalkenes such as LNO₂ and OA-NO₂, derived from reactions of unsaturated fatty acids and oxides of nitrogen, are a class of endogenous anti-inflammatory mediators.

Received for publication, April 7, 2006 , and in revised form, July 21, 2006.

^* This work was supported by National Institutes of Health Grants HL068878, HL075397, and S06GM08248 (to Y. E. C.), HL70146 (to R. P. P.), and HL58115 and HL64937 (to B. A. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1, Fig. 1, and Movie 1.

¹ Supported by American Diabetes Association Grant JFA 7-05-JF-12.

² These authors contributed equally to this work.

³ Supported by the postdoctoral fellowships from the American Heart Association Southeast Affiliate.

⁴ Supported by National Institutes of Health Cardiovascular Hypertension Training Grant T32HL07457.

⁵ To whom correspondence may be addressed. Tel.: 412-648-9319; Fax: 412-648-2229; E-mail: freerad{at}pitt.edu. ⁶ To whom correspondence may be addressed. Tel.: 734-763-7838; Fax: 734-936-2641; E-mail: echenum{at}umich.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. M. Nadtochiy, P. R.S. Baker, B. A. Freeman, and P. S. Brookes Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning: implications for cardioprotection Cardiovasc Res, May 1, 2009; 82(2): 333 - 340. [Abstract] [Full Text] [PDF]

				V. Rudolph, F. J. Schopfer, N. K. H. Khoo, T. K. Rudolph, M. P. Cole, S. R. Woodcock, G. Bonacci, A. L. Groeger, F. Golin-Bisello, C.-S. Chen, et al. Nitro-fatty Acid Metabolome: Saturation, Desaturation, {beta}-Oxidation, and Protein Adduction J. Biol. Chem., January 16, 2009; 284(3): 1461 - 1473. [Abstract] [Full Text] [PDF]

				E. E. Kelley, C. I. Batthyany, N. J. Hundley, S. R. Woodcock, G. Bonacci, J. M. Del Rio, F. J. Schopfer, J. R. Lancaster Jr., B. A. Freeman, and M. M. Tarpey Nitro-oleic Acid, a Novel and Irreversible Inhibitor of Xanthine Oxidoreductase J. Biol. Chem., December 26, 2008; 283(52): 36176 - 36184. [Abstract] [Full Text] [PDF]

				T. Ichikawa, J. Zhang, K. Chen, Y. Liu, F. J. Schopfer, P. R. S. Baker, B. A. Freeman, Y. E. Chen, and T. Cui Nitroalkenes Suppress Lipopolysaccharide-Induced Signal Transducer and Activator of Transcription Signaling in Macrophages: A Critical Role of Mitogen-Activated Protein Kinase Phosphatase 1 Endocrinology, August 1, 2008; 149(8): 4086 - 4094. [Abstract] [Full Text] [PDF]

				B. A. Freeman, P. R. S. Baker, F. J. Schopfer, S. R. Woodcock, A. Napolitano, and M. d'Ischia Nitro-fatty Acid Formation and Signaling J. Biol. Chem., June 6, 2008; 283(23): 15515 - 15519. [Full Text] [PDF]

				L. M. S. Baker, P. R. S. Baker, F. Golin-Bisello, F. J. Schopfer, M. Fink, S. R. Woodcock, B. P. Branchaud, R. Radi, and B. A. Freeman Nitro-fatty Acid Reaction with Glutathione and Cysteine: KINETIC ANALYSIS OF THIOL ALKYLATION BY A MICHAEL ADDITION REACTION J. Biol. Chem., October 19, 2007; 282(42): 31085 - 31093. [Abstract] [Full Text] [PDF]

				C.-C. Hou, Y.-P. Chen, J.-H. Wu, C.-C. Huang, S.-Y. Wang, N.-S. Yang, and L.-F. Shyur A Galactolipid Possesses Novel Cancer Chemopreventive Effects by Suppressing Inflammatory Mediators and Mouse B16 Melanoma Cancer Res., July 15, 2007; 67(14): 6907 - 6915. [Abstract] [Full Text] [PDF]

				L. Villacorta, J. Zhang, M. T. Garcia-Barrio, X.-l. Chen, B. A. Freeman, Y. E. Chen, and T. Cui Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H770 - H776. [Abstract] [Full Text] [PDF]