RT Journal Article T1 Nitric Oxide Down-regulates Caveolin-3 Levels through the Interaction with Myogenin, Its Transcription Factor A1 Martínez-Moreno, Mónica A1 Martínez Ruiz, Antonio A1 Álvarez-Barrientos, Alberto A1 Gavilanes Franco, Francisco A1 Lamas, Santiago A1 Rodríguez Crespo, José Ignacio AB 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 previouslyreported 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. SN 0021-9258 YR 2007 FD 2007-08 LK https://hdl.handle.net/20.500.14352/102742 UL https://hdl.handle.net/20.500.14352/102742 LA eng DS Docta Complutense RD 10 abr 2025