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Glutathione peroxidase 3, a new retinoid target gene, is critical for human skeletal muscle precursor cell survival.
MedLine Citation:
PMID:  23132926     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Protection of satellite cells from cytotoxic damages is a critical issue 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 these cytotoxic damages 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, a gene encoding an antioxidant enzyme, as a potential retinoic acid target gene in human myoblasts. Knockdown of glutathione peroxidase 3 via siRNA 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:
Marina El Haddad; Elise Jean; Ahmed Turki; Gérald Hugon; Barbara Vernus; Anne Bonnieu; Emilie Passerieux; Aline Hamade; Jacques Mercier; Dalila Laoudj-Chenivesse; Gilles Carnac
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-6
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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