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Article Dans Une Revue General and Comparative Endocrinology Année : 2013

Myostatin induces atrophy of trout myotubes through inhibiting the TORC1 signaling and promoting ubiquitin-proteasome and autophagy-lysosome degradative pathways

Résumé

Myostatin (MSTN) is well known as a potent inhibitor of muscle growth in mammals and has been shown to both inhibit the growth promoting TORC1 signaling pathway and promote Ubiquitin–Proteasomal and Autophagy-Lysosomal degradative routes . In contrast, in non-mammalian species, despite high structural conservation of MSTN sequence, functional conservation is only assumed . Here, we show that treatment of cultured trout myotubes with human recombinant MSTN (huMSTN) resulted in a significant decrease of their diamet er by up to 20%, validating the use of heterologous huMSTN in our in vitro model to monitor the processes by which this growth factor promote s muscle wasting in fish. Accordingly, huMSTN stimulation prevented the full activation by IGF1 of the TORC1 signaling pathway, as revealed by the analysis of the phosphorylation status of 4E-BP1. Moreover, the levels of the proteasome-depe ndent protein Atrogin1 exhibited an increase in huMSTN treated cells. Likewise, we observed a stimulatory effect of huMSTN treatment on the levels of LC3-II, the more reliable marker of the Autophagy-Lysosomal degradative system. Overall, these results show for the first time in a piscine species the effect of MSTN on several atrophic and hypertrophic pathways and support a functional conserv ation of this growth factor between lower and higher vertebrates.

Domaines

Biologie animale
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Dates et versions

hal-01205067 , version 1 (24-09-2015)

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Iban Seiliez, Gemael Cedrick Taty Taty, Jérôme Bugeon, Karine Dias, Nathalie Sabin, et al.. Myostatin induces atrophy of trout myotubes through inhibiting the TORC1 signaling and promoting ubiquitin-proteasome and autophagy-lysosome degradative pathways. General and Comparative Endocrinology, 2013, 186, pp.9-15. ⟨10.1016/j.ygcen.2013.02.008⟩. ⟨hal-01205067⟩
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