Document Detail


Impaired myogenesis in estrogen-related receptor γ (ERRγ)-deficient skeletal myocytes due to oxidative stress.
MedLine Citation:
PMID:  23038752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-ERRγWT) and muscle-specific ERRγ(-/-) (M-ERRγ(-/-)) mice. Myotube maturation and number were decreased throughout differentiation in M-ERRγ(-/-) primary myocytes, resulting in myotubes with reduced mitochondrial content and sarcomere assembly. Compared with M-ERRγWT myocytes at the same differentiation stage, the glucose oxidation rate was reduced by 30% in M-ERRγ(-/-) myotubes, while medium-chain fatty acid oxidation was increased by 34% in M-ERRγ(-/-) myoblasts and 36% in M-ERRγ(-/-) myotubes. Concomitant with increased reliance on mitochondrial β-oxidation, H(2)O(2) production was significantly increased by 40% in M-ERRγ(-/-) myoblasts and 70% in M-ERRγ(-/-) myotubes compared to M-ERRγWT myocytes. ROS activation of FoxO and NF-κB and their downstream targets, atrogin-1 and MuRF1, was observed in M-ERRγ(-/-) myocytes. The antioxidant N-acetyl cysteine rescued myotube formation and atrophy gene induction in M-ERRγ(-/-) myocytes. These results suggest that loss of ERRγ causes metabolic defects and oxidative stress that impair myotube formation through activation of skeletal muscle atrophy pathways.
Authors:
Jennifer Murray; Johan Auwerx; Janice M Huss
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-07     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  135-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blotting, Western
DNA Primers
Mice
Muscle Development*
Muscle, Skeletal / cytology,  metabolism,  physiology*
Oxidative Stress*
Real-Time Polymerase Chain Reaction
Receptors, Estrogen / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
R01DK074700/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Esrrg protein, mouse; 0/Receptors, Estrogen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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