title: Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival.
abstract: Protection of satellite cells from cytotoxic damages is crucial to ensure efficient adult skeletal muscle regeneration and to improve therapeutic efficacy of cell transplantation in degenerative skeletal muscle diseases. It is therefore important to identify and characterize molecules and their target genes that control the viability of muscle stem cells. Recently, we demonstrated that high aldehyde dehydrogenase activity is associated with increased viability of human myoblasts. In addition to its detoxifying activity, aldehyde dehydrogenase can also catalyze the irreversible oxidation of vitamin A to retinoic acid; therefore, we examined whether retinoic acid is important for myoblast viability. We showed that when exposed to oxidative stress induced by hydrogen peroxide, adherent human myoblasts entered apoptosis and lost their capacity for adhesion. Pre-treatment with retinoic acid reduced the cytotoxic damage ex vivo and enhanced myoblast survival in transplantation assays. The effects of retinoic acid were maintained in dystrophic myoblasts derived from facioscapulohumeral patients. RT-qPCR analysis of antioxidant gene expression revealed glutathione peroxidase 3 (Gpx3), a gene encoding an antioxidant enzyme, as a potential retinoic acid target gene in human myoblasts. Knockdown of Gpx3 using short interfering RNA induced elevation in reactive oxygen species and cell death. The anti-cytotoxic effects of retinoic acid were impaired in GPx3-inactivated myoblasts, which indicates that GPx3 regulates the antioxidative effects of retinoic acid. Therefore, retinoid status and GPx3 levels may have important implications for the viability of human muscle stem cells.
authors.affiliation: Inserm U1046, Université Montpellier 1, 34295 Montpellier, France.
authors.forename: Marina
authors.initials: M
authors.lastname: El Haddad
authors.forename: Elise
authors.initials: E
authors.lastname: Jean
authors.forename: Ahmed
authors.initials: A
authors.lastname: Turki
authors.forename: Gérald
authors.initials: G
authors.lastname: Hugon
authors.forename: Barbara
authors.initials: B
authors.lastname: Vernus
authors.forename: Anne
authors.initials: A
authors.lastname: Bonnieu
authors.forename: Emilie
authors.initials: E
authors.lastname: Passerieux
authors.forename: Aline
authors.initials: A
authors.lastname: Hamade
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Dalila
authors.initials: D
authors.lastname: Laoudj-Chenivesse
authors.forename: Gilles
authors.initials: G
authors.lastname: Carnac
mesh_terms: D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014212:Tretinoin; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase