Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy (Articolo in rivista)

Type
Label
  • Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1172/JCI66339 (literal)
Alternative label
  • Zaglia T.; Milan G.; Ruhs A.; Franzoso M.; Bertaggia E.; Pianca N.; Carpi A.; Carullo P.; Pesce P.; Sacerdoti D.; Sarais C.; Catalucci D.; Kruger M.; Mongillo M.; Sandri M. (2014)
    Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy
    in The journal of clinical investigation (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Zaglia T.; Milan G.; Ruhs A.; Franzoso M.; Bertaggia E.; Pianca N.; Carpi A.; Carullo P.; Pesce P.; Sacerdoti D.; Sarais C.; Catalucci D.; Kruger M.; Mongillo M.; Sandri M. (literal)
Pagina inizio
  • 2410 (literal)
Pagina fine
  • 2424 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.scopus.com/inward/record.url?eid=2-s2.0-84902208708&partnerID=q2rCbXpz (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 124 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 6 (literal)
Note
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Biomedical Sciences, University of Padova, Padova, Italy; Molecular Cardiology, Venetian Institute of Molecular Medicine, via Orus 2, 35129 Padova, Italy; Muscle Signaling Lab., Venetian Institute of Molecular Medicine, via Orus 2, 35129 Padova, Italy; Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; European Institute of Oncology, Milan, Italy; National Research Council (CNR), Institute of Genetic and Biomedical Research - UOS of Milan, Milan, Italy; Humanitas Clinical and Research Center, Milan, Italy; Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy; Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy; CNR, Institute of Neuroscience, Padova, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy (literal)
Titolo
  • Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy (literal)
Abstract
  • Cardiomyocyte proteostasis is mediated by the ubiquitin/proteasome system (UPS) and autophagy/lysosome system and is fundamental for cardiac adaptation to both physiologic (e.g., exercise) and pathologic (e.g., pressure overload) stresses. Both the UPS and autophagy/lysosome system exhibit reduced efficiency as a consequence of aging, and dysfunction in these systems is associated with cardiomyopathies. The musclespecific ubiquitin ligase atrogin-1 targets signaling proteins involved in cardiac hypertrophy for degradation. Here, using atrogin-1 KO mice in combination with in vivo pulsed stable isotope labeling of amino acids in cell culture proteomics and biochemical and cellular analyses, we identified charged multivesicular body protein 2B (CHMP2B), which is part of an endosomal sorting complex (ESCRT) required for autophagy, as a target of atrogin-1-mediated degradation. Mice lacking atrogin-1 failed to degrade CHMP2B, resulting in autophagy impairment, intracellular protein aggregate accumulation, unfolded protein response activation, and subsequent cardiomyocyte apoptosis, all of which increased progressively with age. Cellular proteostasis alterations resulted in cardiomyopathy characterized by myocardial remodeling with interstitial fibrosis, with reduced diastolic function and arrhythmias. CHMP2B downregulation in atrogin-1 KO mice restored autophagy and decreased proteotoxicity, thereby preventing cell death. These data indicate that atrogin-1 promotes cardiomyocyte health through mediating the interplay between UPS and autophagy/lysosome system and its alteration promotes development of cardiomyopathies. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it