Résumé :
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Oxygen availability plays a central role during early development and normal muscular activity. Hypoxia, a decrease in oxygen availability, seems to induce modifications in the main calcineurin, PI3K and p38-MAPK pathways. To examine the hypoxia-induced alterations in these pathways during myogenesis, two models were used, in vitro differentiation of myoblasts and in vivo myogenesis during early development.In culture cells (L6 rat cells), hypoxia perturbs the myoblast differentiation, reduces myotubes size, modifies the fusion index and affects the signalling of AKT, p38-MAPK and calcineurin pathways. Hypoxia also affects phosphorylation of the S6 translation factor, downstream mTOR, without affecting the 4E-BP1 translation factor. In the embryo (Xenopus laevis), hypoxia causes growth retardation and affects differentiation of myotomes. This effect is correlated to an activation of p38-MAPK and a decreased in the phosphorylated AKT level, associated downstream with a cytoplasmic accumulation of the 4E-BP1 translation factor. This accumulation is observed in axial tissues such as the notochord and somites. The data also show that in vivo, the 4E-BP1 reversibly inhibits the cap-dependent translation of mRNA. The effects of hypoxia on the main intracellular PI3K, p38-MAPK and Calcineurin pathways are discussed by comparing data acquired on both systems.* This work was supported by the Association Franse contre les Myopathies (AFM, grant N°1395).
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