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oai:docta.ucm.es:20.500.14352/1027422024-04-05T23:53:30Zcom_20.500.14352_14col_20.500.14352_15

Nitric Oxide Down-regulates Caveolin-3 Levels through the Interaction with Myogenin, Its Transcription Factor Martínez-Moreno, Mónica Martínez Ruiz, Antonio Álvarez-Barrientos, Alberto Gavilanes Franco, Francisco Lamas, Santiago Rodríguez Crespo, José Ignacio 577.1 Bioquímica (Farmacia) 2302 Bioquímica Certain patients suffering from chronic diseases such as AIDS or cancer experience a constant cellular secretion of tumor necrosis factor and other pro-inflammatory cytokines that results in a continuous release of nitric oxide ( NO) to the bloodstream. One immediate consequence of the deleterious action of NO is weight loss and the progressive destruction of muscular mass in a process known as cachexia. We have previously reported that caveolin-3, a specific marker of muscle cells, becomes down-regulated by the action of NO on muscular myotubes. We describe herein that the changes observed in caveolin-3 levels are due to the alteration of the DNA binding activity of the muscular transcription factor myogenin. In the presence of NO, the binding of transcription factors from cell nuclear extracts of muscular tissues to the E boxes present in the caveolin-3 promoter become substantially reduced.When we purified recombinant myogenin and treated it with NO donors, we could detect its S-nitrosylation by three independent methods, suggesting that very likely one of the cysteine residues of the molecule is being modified. Given the role of myogenin as a regulatory protein that determines the level of multiple muscle genes expressed during late myogenesis, our results might represent a novel mode of regulation of muscle development under conditions of nitric oxide-mediated toxicity. Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2024-04-05T10:48:37Z 2024-04-05T10:48:37Z 2007-08 journal article AM https://hdl.handle.net/20.500.14352/102742 0021-9258 10.1074/jbc.m610751200 eng Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ open access application/pdf