Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival
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 targ...
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Published in | Journal of cell science Vol. 125; no. Pt 24; pp. 6147 - 6156 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Company of Biologists
15.12.2012
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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. |
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AbstractList | 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. |
Author | Hamade, Aline Vernus, Barbara Mercier, Jacques Passerieux, Emilie Jean, Elise Laoudj-Chenivesse, Dalila Carnac, Gilles El Haddad, Marina Turki, Ahmed Bonnieu, Anne Hugon, Gérald |
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Keywords | myoblasts retinoic acid vitamin A GPx3 facioscapulohumeral dystrophy (FSHD) transplantation |
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SubjectTerms | Adult Animals Antioxidants - pharmacology Apoptosis Cell Survival - drug effects Cell Survival - genetics Cells, Cultured Gene Knockdown Techniques Glutathione Peroxidase - deficiency Glutathione Peroxidase - genetics Glutathione Peroxidase - metabolism Humans Life Sciences Mice Mice, SCID Myoblasts - cytology Myoblasts - drug effects Myoblasts - enzymology Reactive Oxygen Species - metabolism Tretinoin - pharmacology |
Title | Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival |
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