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Báo cáo khoa học: The endogenous retinoid metabolite S-4-oxo-9-cis-13,14-dihydro-retinoic acid activates retinoic acid receptor signalling both in vitro and in vivo

Retinoic acid receptor (RAR) and retinoid X receptor are ligand-induced transcription factors that belong to the nuclear receptor family. The receptors are activated by small hydrophobic compounds, such as all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Interestingly, these receptors are also targets for a number of exogenous compounds. | ỊFEBS Journal The endogenous retinoid metabolite S-4-oxo-9-cis-13 14-dihydro-retinoic acid activates retinoic acid receptor signalling both in vitro and in vivo Jan P. Schuchardt1 David Wahlstrom2 Joelle Ruegg2 Norbert Giese1 Madalina Stefan3 Henning Hopf3 Ingemar Pongratz2 Helen Hakansson4 Gregor Eichele5 Katarina Pettersson2 and Heinz Nau1 1 Institute for Food Toxicology and AnalyticalChemistry University of Veterinary Medicine Hannover Germany 2 Department of Biosciences and Nutrition Karolinska Institutet Huddinge Sweden 3 Institute of Organic Chemistry TechnicalUniversity Braunschweig Germany 4 Institute of EnvironmentalMedicine Karolinska Institutet Stockholm Sweden 5 Max-Planck-Institute for BiophysicalChemistry Gottingen Germany Keywords dihydro-retinoic acid metabolite gene expression novelretinoid metabolites RAR vitamin A metabolism Correspondence J. P. Schuchardt Institute of Food Science Leibniz University of Hannover Am Kleinen Felde 30 30167 Hannover Germany Fax 49 511 762 5729 Tel 49 511 762 2987 E-mail jan-philipp.schuchardt@lw. uni-hannover.de Received 16 December 2008 revised 3 March 2009 accepted 25 March 2009 doi 10.1111 j.1742-4658.2009.07023.x Retinoic acid receptor RAR and retinoid X receptor are ligand-induced transcription factors that belong to the nuclear receptor family. The receptors are activated by small hydrophobic compounds such as all-trans-retinoic acid and 9-cis-retinoic acid respectively. Interestingly these receptors are also targets for a number of exogenous compounds. In this study we characterized the biological activity of the 9-cis-substituted retinoic acid metabolite S-4-oxo-9-cis-13 14-dihydro-retinoic acid S-4o9cDH-RA . The endogenous levels of this metabolite in wild-type mice and rats were found to be higher than those of all-trans-retinoic acid especially in the liver. Using cell-based luciferase reporter systems we showed that S-4o9cDH-RA activates the transcription of retinoic acid response element-containing .