Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques

Am J Physiol Regul Integr Comp Physiol. 2014 Jun 1;306(11):R837-44. doi: 10.1152/ajpregu.00502.2013. Epub 2014 Mar 26.


Chronic alcohol abuse is associated with skeletal muscle myopathy. Previously, we demonstrated that chronic binge alcohol (CBA) consumption by rhesus macaques accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus (SIV) infection. A proinflammatory, prooxidative milieu and enhanced ubiquitin proteasome activity were identified as possible mechanisms leading to loss of skeletal muscle. The possibility that impaired regenerative capacity, as reflected by the ability of myoblasts derived from satellite cell (SCs) to differentiate into myotubes has not been examined. We hypothesized that the inflammation and oxidative stress in skeletal muscle from CBA animals impair the differentiation capacity of myoblasts to form new myofibers in in vitro assays. We isolated primary myoblasts from the quadriceps femoris of rhesus macaques that were administered CBA or isocaloric sucrose (SUC) for 19 mo. Proliferation and differentiation potential of cultured myoblasts were examined in vitro. Myoblasts from the CBA group had significantly reduced PAX7, MYOD1, MYOG, MYF5, and MEF2C expression. This was associated with decreased myotube formation as evidenced by Jenner-Giemsa staining and myonuclei fusion index. No significant difference in the proliferative ability, cell cycle distribution, or autophagy was detected between myoblasts isolated from CBA and SUC groups. Together, these results reflect marked dysregulation of myoblast myogenic gene expression and myotube formation, which we interpret as evidence of impaired skeletal muscle regenerative capacity in CBA-administered macaques. The contribution of this mechanism to alcoholic myopathy warrants further investigation.

Keywords: chronic binge alcohol; gene expression; myoblasts; myogenic differentiation; rhesus macaques; satellite cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Animals
  • Binge Drinking / physiopathology*
  • Cell Differentiation / physiology*
  • Cell Proliferation
  • Gene Expression Regulation / physiology*
  • In Vitro Techniques
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / physiology
  • Macaca mulatta / physiology*
  • Male
  • Models, Animal
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • MyoD Protein / genetics
  • MyoD Protein / physiology
  • Myoblasts, Skeletal / pathology*
  • Myoblasts, Skeletal / physiology
  • Myogenic Regulatory Factor 5 / genetics
  • Myogenic Regulatory Factor 5 / physiology
  • Myogenin / genetics
  • Myogenin / physiology
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / physiology


  • MEF2 Transcription Factors
  • Muscle Proteins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenic Regulatory Factor 5
  • Myogenin
  • PAX7 Transcription Factor