%0 Journal Article %T Electrophilic fatty acids regulate matrix metalloproteinase activity and expression. %+ Department of Pharmacology and Chemical Biology %+ Institut Pasteur de Montevideo %+ Department of Cardiology %+ Department of Anesthesiology %A Bonacci, Gustavo %A Schopfer, Francisco J %A Batthyany, Carlos I %A Rudolph, Tanja K %A Rudolph, Volker %A Khoo, Nicholas K H %A Kelley, Eric E %A Freeman, Bruce A %Z This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL58115 and R01 HL64937 (to B. A. F.), American Diabetes Association Grant 7-08-JF-52 (to F. J. S.), American Heart Association Grant 0665418U (to F. J. S.), and a grant from the Deutsche Herzstiftung (to V. R.). B. A. F. acknowledges financial interest in Complexa, Inc. %< avec comité de lecture %@ 0021-9258 %J Journal of Biological Chemistry %I American Society for Biochemistry and Molecular Biology %V 286 %N 18 %P 16074-81 %8 2011-05-06 %D 2011 %R 10.1074/jbc.M111.225029 %M 21454668 %Z Life Sciences [q-bio]/Biochemistry, Molecular BiologyJournal articles %X Nitro-fatty acids (NO(2)-FA) are electrophilic signaling mediators formed by reactions of nitric oxide and nitrite. NO(2)-FA exert anti-inflammatory signaling actions through post-translational protein modifications. We report that nitro-oleic acid (OA-NO(2)) stimulates proMMP-7 and proMMP-9 proteolytic activity via adduction of the conserved cysteine switch domain thiolate. Biotin-labeled OA-NO(2) showed this adduction occurs preferentially with latent forms of MMP, confirming a role for thiol alkylation by OA-NO(2) in MMP activation. In addition to regulating pro-MMP activation, MMP expression was modulated by OA-NO(2) via activation of peroxisome proliferator-activated receptor-γ. MMP-9 transcription was decreased in phorbol 12-myristate 13-acetate-stimulated THP-1 macrophages to an extent similar to that induced by the peroxisome proliferator-activated receptor-γ agonist Rosiglitazone. This was affirmed using a murine model of atherosclerosis, ApoE(-/-) mice, where in vivo OA-NO(2) administration suppressed MMP expression in atherosclerotic lesions. These findings reveal that electrophilic fatty acid derivatives can serve as effectors during inflammation, first by activating pro-MMP proteolytic activity via alkylation of the cysteine switch domain, and then by transcriptionally inhibiting MMP expression, thereby limiting the further progression of inflammatory processes. %G English %L pasteur-00685059 %U https://riip.hal.science/pasteur-00685059 %~ RIIP %~ RIIP_MONTEVIDEO