PloS one, 2012-10, Vol.7 (10), p.e46427-e46427
2012
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- Autor(en) / Beteiligte
- Titel
- The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice
- Ist Teil von
- PloS one, 2012-10, Vol.7 (10), p.e46427-e46427
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Skeletal muscle atrophy is a consequence of muscle inactivity resulting from denervation, unloading and immobility. It accompanies many chronic disease states and also occurs as a pathophysiologic consequence of normal aging. In all these conditions, ubiquitin-dependent proteolysis is a key regulator of the loss of muscle mass, and ubiquitin ligases confer specificity to this process by interacting with, and linking ubiquitin moieties to target substrates through protein:protein interaction domains. Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and immobility). Here we generated a novel tool, the Nedd4-1 skeletal muscle-specific knockout mouse (myo(Cre);Nedd4-1(flox/flox)) and subjected it to a well validated model of denervation induced skeletal muscle atrophy. The absence of Nedd4-1 resulted in increased weights and cross-sectional area of type II fast twitch fibres of denervated gastrocnemius muscle compared with wild type littermates controls, at seven and fourteen days following tibial nerve transection. These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0046427Titel-ID: cdi_plos_journals_1326561089
- Format
- –
- Schlagworte
- Aging, Animals, Atrophy, Biology, Blotting, Western, Cells, Cultured, Chronic diseases, Chronic illnesses, Chronic obstructive pulmonary disease, Denervation, Endosomal Sorting Complexes Required for Transport - genetics, Endosomal Sorting Complexes Required for Transport - metabolism, Enzymes, Female, Fibroblast growth factor receptor 1, Flox, Gastrocnemius muscle, Immunohistochemistry, Kinases, Ligases, Male, Medicine, Mice, Mice, Knockout, Muscle Denervation, Muscles, Muscular Atrophy - genetics, Muscular Atrophy - metabolism, Musculoskeletal system, Myoblasts - cytology, Myoblasts - metabolism, Nedd4 Ubiquitin Protein Ligases, Neurobiology, Neurosciences, Notch1 protein, Phosphatase, Protein Tyrosine Phosphatases, Non-Receptor - genetics, Protein Tyrosine Phosphatases, Non-Receptor - metabolism, Proteins, Proteolysis, Receptor, Fibroblast Growth Factor, Type 1 - genetics, Receptor, Fibroblast Growth Factor, Type 1 - metabolism, Receptor, Notch1 - genetics, Receptor, Notch1 - metabolism, Rodents, Satellite Cells, Skeletal Muscle - cytology, Satellite Cells, Skeletal Muscle - metabolism, Skeletal muscle, Substrates, Tibial nerve, Ubiquitin, Ubiquitin-protein ligase, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism, Unloading