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Title

Nitric oxide down-regulates caveolin-3 levels through the interaction with myogenin, its transcription factor

AuthorsMartínez-Moreno, Mónica; Martínez-Ruiz, Antonio ; Álvarez Barrientos, Alberto; Gavilanes, Francisco; Lamas Peláez, Santiago ; Rodríguez-Crespo, Ignacio
Issue Date10-Aug-2007
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJ Biol Chem. 282(32):23044-54 (2007)
AbstractCertain patients suffering from chronic diseases such as AIDS or cancer experience a constant cellular secretion of tumor necrosis factor α 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.
Description12 p.-7 fig.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M610751200
URIhttp://hdl.handle.net/10261/160689
DOI10.1074/jbc.M610751200
ISSN0021-9258
E-ISSN1083-351X
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