Résumé :
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Selenoprotein N (SelN; encoded by SEPN1 gene) is the only selenoprotein associated to a human genetic disease, SEPN1-related myopathy (SEPN1-RM), which is typified by severe weakness and wasting of neck and trunk muscles. In SelN-/- mice, there is a reduced rate of muscle repair and a depletion of the satellite cell (SC) population after injury when compared to wild-type mice, suggesting that SelN is important for maintaining the balance between self-renewal and differentiation of the SCs. Congruently, we observe an accelerated initiation of cell differentiation and perturbations in the level and subcellular localisation of myogenic regulating and cell cycle exit factors in C2C12 cells treated with SEPN1 siRNA. These data go a long way to explaining the patients' phenotype; however, the exact function of SelN is still unknown. We have previously demonstrated that, in human muscle cells devoid of SelN, there is an increase in intracellular oxidant activity and protein carbonylation. Additionally, using our siRNA silencing system, SelN devoid muscle cells have a specific misregulation of antioxidant genes. This suggests that SelN is important for maintaining the general redox state of the cell, but in a very precise manner. As the link between oxidative stress and differentiation is undefined, but undoubtedly exists, it is important for us to clearly determine the underlying mechanism by which SelN functions.
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