Résumé
Abstract only Mutations of the selenoprotein N gene ( SEPN1 ) have been identified as responsible for SEPN‐related myopathy (SEPN‐RM), an early‐onset muscle disorder. Selenoprotein N is the only selenoprotein implicated in a human genetic disorder but its function remained unknown. SelN has structural similarities with other selenoproteins which are involved in redox homeostasis. Therefore, we hypothesized that 1/ SelN depletion increase intracellular oxidant activity in cells, 2/ SelN plays a role in defence against oxidative stress. To verify this, we used human primary myoblasts and fibroblasts cultures from controls and patients carrying nonsense SEPN1 mutations. We measured intracellular oxidant activity using the DCFH assay. Furthermore, we examined the susceptibility of the cells to a wide range of H 2 O 2 concentrations. Myoblasts devoid of SelN show a significant increase in intracellular oxidant activity compared to controls whereas fibroblasts do not. However, fibroblasts devoid of SelN are more sensitive to H 2 O 2 ‐induced oxidative stress than normal fibroblasts, as evidenced by a significantly greater cell death. Furthermore, pre‐treatment with the antioxidant N‐acetyl cysteine restores cell survival against H 2 O 2 to a level comparable to controls. This study establishes for the first time that oxidative stress is implicated in SEPN‐RM and that SelN protects human cells against oxidative stress.