Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2.
Biochim Biophys Acta
; 1853(7): 1606-14, 2015 Jul.
Article
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| MEDLINE
| ID: mdl-25827955
ABSTRACT
Rotenone (ROT) is a widely used inhibitor of complex I (CI), the first complex of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, particularly at high concentrations ROT was also described to display off-target effects. Here we studied how ROT affected in vitro primary murine myotube formation. We demonstrate that myotube formation is specifically inhibited by ROT (10-100nM), but not by piericidin A (PA; 100nM), another CI inhibitor. At 100nM, both ROT and PA fully blocked myoblast oxygen consumption. Knock-down of Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and, to a lesser extent ROCK1, prevented the ROT-induced inhibition of myotube formation. Moreover, the latter was reversed by inhibiting Raf-1 activity. In contrast, ROT-induced inhibition of myotube formation was not prevented by knock-down of RhoA. Taken together, our results support a model in which ROT reduces primary myotube formation independent of its inhibitory effect on CI-driven mitochondrial ATP production, but via a mechanism primarily involving the Raf-1/ROCK2 pathway.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rotenona
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Fibras Musculares Esqueléticas
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Proteínas Proto-Oncogénicas c-raf
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Desarrollo de Músculos
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Quinasas Asociadas a rho
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos