title: Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques.
abstract: 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.
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana;
authors.forename: Liz
authors.initials: L
authors.lastname: Simon
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; Comprehensive Alcohol Research Center, Louisiana State University, Health Sciences Center, New Orleans, Lousiana;
authors.forename: Nicole
authors.initials: N
authors.lastname: LeCapitaine
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana;
authors.forename: Paul
authors.initials: P
authors.lastname: Berner
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana;
authors.forename: Curtis
authors.initials: C
authors.lastname: Vande Stouwe
authors.affiliation: Department of Cell Biology and Anatomy, Pennington Biomedical Research Center, Baton Rouge, Louisiana;
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mussell
authors.affiliation: Joint Program on Diabetes, Endocrinology, and Metabolism, Pennington Biomedical Research Center, Baton Rouge and Louisiana State University, Health Sciences Center, New Orleans, Louisiana;
authors.forename: Timothy
authors.initials: T
authors.lastname: Allerton
authors.affiliation: Joint Program on Diabetes, Endocrinology, and Metabolism, Pennington Biomedical Research Center, Baton Rouge and Louisiana State University, Health Sciences Center, New Orleans, Louisiana;
authors.forename: Stefany D
authors.initials: SD
authors.lastname: Primeaux
authors.affiliation: Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana; and.
authors.forename: Jason
authors.initials: J
authors.lastname: Dufour
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; Comprehensive Alcohol Research Center, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; School of Medicine, Louisiana State University, Health Sciences Center, New Orleans, Louisiana.
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; Comprehensive Alcohol Research Center, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; School of Medicine, Louisiana State University, Health Sciences Center, New Orleans, Louisiana.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.affiliation: Joint Program on Diabetes, Endocrinology, and Metabolism, Pennington Biomedical Research Center, Baton Rouge and Louisiana State University, Health Sciences Center, New Orleans, Louisiana;
authors.forename: William
authors.initials: W
authors.lastname: Cefalu
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; Comprehensive Alcohol Research Center, Louisiana State University, Health Sciences Center, New Orleans, Lousiana; pmolin@lsuhsc.edu.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D063425:Binge Drinking / Q000503:physiopathology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000502:physiology; D008253:Macaca mulatta / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000473:pathology* / Q000502:physiology; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000502:physiology; D018008:Myogenin / Q000235:genetics / Q000502:physiology; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000502:physiology
chemical_list: D064326:MEF2 Transcription Factors; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D051763:PAX7 Transcription Factor
keywords: chronic binge alcohol; gene expression; myoblasts; myogenic differentiation; rhesus macaques; satellite cells