An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart. (Articolo in rivista)

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  • An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart. (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Alternative label
  • Eva Tritsch1, Youssef Mallat1, Florence Lefebvre2,3, Nicolas Diguet1, Brigitte Escoubet4,5, Jocelyne Blanc1, Leon J. De Windt6, Daniele Catalucci7,8, Grégoire Vandecasteele2,3, Zhenlin Li1 and Mathias Mericskay1,* (2013)
    An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart.
    in Cardiovascular research (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Eva Tritsch1, Youssef Mallat1, Florence Lefebvre2,3, Nicolas Diguet1, Brigitte Escoubet4,5, Jocelyne Blanc1, Leon J. De Windt6, Daniele Catalucci7,8, Grégoire Vandecasteele2,3, Zhenlin Li1 and Mathias Mericskay1,* (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Department of Aging, Stress and Inflammation (UR4), UPMC Univ Paris 6, 7, quai Saint Bernard - BP 256, Paris 75005, France 2Inserm UMR-S 769, LabEx LERMIT, Châtenay-Malabry 92296, France 3University Paris-Sud, IFR141, Châtenay-Malabry 92296, France 4Univ Paris Diderot, Sorbonne Paris Cité, CEFI, Paris F-75018, France 5Inserm, UMR 872, Centre de Recherche des Cordeliers CRC, Paris F-75006, France 6Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands 7Biomedical and Genetic Research Institute, National Research Council, Milan, Italy 8Humanitas Clinical and Research Center, Rozzano, Milan, Italy (literal)
Titolo
  • An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart. (literal)
Abstract
  • Aims The expression of the sodium/calcium exchanger NCX1 increases during cardiac hypertrophy and heart failure, playing an important role in Ca2+ extrusion. This increase is presumed to result from stress signalling induced changes in the interplay between transcriptional and post-transcriptional regulations. We aimed to determine the impact of the SRF transcription factor known to regulate the NCX1 promoter and microRNA genes, on the expression of NCX1 mRNA and protein and Annexin A5 (AnxA5), a Ca2+-binding protein interacting with NCX1 and increased during HF. Methods and results NCX1 mRNA was decreased while the protein was increased in the failing heart of the cardiomyocyte-restricted SRF knock-out mice (SRFHKO). The induction of NCX1 mRNA by the pro-hypertrophic drug phenylephrine observed in control mice was abolished in the SRFHKO though the protein was strongly increased. AnxA5 protein expression profile paralleled the expression of NCX1 protein in the SRFHKO. MiR-1, a microRNA regulated by SRF, was decreased in the SRFHKO and repressed by phenylephrine. In vitro and in vivo manipulation of miR-1 levels and site-directed mutagenesis showed that NCX1 and AnxA5 mRNAs are targets of miR-1. AnxA5 overexpression slowed down Ca2+ extrusion during caffeine application in adult rat cardiomyocytes. Conclusion Our study reveals the existence of a complex regulatory loop where SRF regulates the transcription of NCX1 and miR-1, which in turn functions as a rheostat limiting the translation of NCX1 and AnxA5 proteins. The decrease of miR-1 and increase of AnxA5 appear as important modulators of NCX1 expression and activity during heart failure. (literal)
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