title: Myostatin induces atrophy of trout myotubes through inhibiting the TORC1 signaling and promoting Ubiquitin-Proteasome and Autophagy-Lysosome degradative pathways.
abstract: 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 diameter by up to 20%, validating the use of heterologous huMSTN in our in vitro model to monitor the processes by which this growth factor promotes 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-dependent 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 conservation of this growth factor between lower and higher vertebrates.
authors: INRA, UMR1067 Nutrition Métabolisme et Aquaculture, Pôle d'hydrobiologie, CD918, F-64310 St-Pée-sur-Nivelle, France. seiliez@st-pee.inra.fr
authors: Iban
authors: I
authors: Seiliez
authors: Gémaël Cédrick
authors: GC
authors: Taty Taty
authors: Jérôme
authors: J
authors: Bugeon
authors: Karine
authors: K
authors: Dias
authors: Nathalie
authors: N
authors: Sabin
authors: Jean-Charles
authors: JC
authors: Gabillard
mesh_terms: D000818:Animals; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D055435:Myostatin / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014337:Trout; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D055435:Myostatin; D025801:Ubiquitin; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex