| First Author | Murray J | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 1 | Pages | 135-50 |
| PubMed ID | 23038752 | Mgi Jnum | J:318168 |
| Mgi Id | MGI:6858541 | Doi | 10.1096/fj.12-212290 |
| Citation | Murray J, et al. (2013) Impaired myogenesis in estrogen-related receptor gamma (ERRgamma)-deficient skeletal myocytes due to oxidative stress. FASEB J 27(1):135-50 |
| abstractText | Specialized contractile function and increased mitochondrial number and oxidative capacity are hallmark features of myocyte differentiation. The estrogen-related receptors (ERRs) can regulate mitochondrial biogenesis or mitochondrial enzyme expression in skeletal muscle, suggesting that ERRs may have a role in promoting myogenesis. Therefore, we characterized myogenic programs in primary myocytes isolated from wild-type (M-ERRgammaWT) and muscle-specific ERRgamma(-/-) (M-ERRgamma(-/-)) mice. Myotube maturation and number were decreased throughout differentiation in M-ERRgamma(-/-) primary myocytes, resulting in myotubes with reduced mitochondrial content and sarcomere assembly. Compared with M-ERRgammaWT myocytes at the same differentiation stage, the glucose oxidation rate was reduced by 30% in M-ERRgamma(-/-) myotubes, while medium-chain fatty acid oxidation was increased by 34% in M-ERRgamma(-/-) myoblasts and 36% in M-ERRgamma(-/-) myotubes. Concomitant with increased reliance on mitochondrial beta-oxidation, H(2)O(2) production was significantly increased by 40% in M-ERRgamma(-/-) myoblasts and 70% in M-ERRgamma(-/-) myotubes compared to M-ERRgammaWT myocytes. ROS activation of FoxO and NF-kappaB and their downstream targets, atrogin-1 and MuRF1, was observed in M-ERRgamma(-/-) myocytes. The antioxidant N-acetyl cysteine rescued myotube formation and atrophy gene induction in M-ERRgamma(-/-) myocytes. These results suggest that loss of ERRgamma causes metabolic defects and oxidative stress that impair myotube formation through activation of skeletal muscle atrophy pathways. |
