A novel cell-based system for evaluating skeletal muscle cell hypertrophy-inducing agents.
Skeletal muscle is a tissue that adapts to increased use by increasing contractile protein gene expression and ultimately skeletal muscle mass (hypertrophy). To identify hypertrophy-inducing agents that may be potentially useful in the treatment of age-related muscle loss (sarcopenia) and to better understand hypertrophy signal transduction pathways, we have created a skeletal muscle cell-based hypertrophy-responsive system. This system was created by permanently modifying the relatively undifferentiated C2C12 cell line so that it contains the beta-myosin heavy chain (beta-MHC) gene promoter and enhancer regions fused to a luciferase reporter gene. This cell line responds, by increasing luciferase expression, to a variety of skeletal muscle hypertrophy-inducing agents, including insulin, insulin-like growth factor I, testosterone, and the beta-adrenergic receptor agonist isoproterenol, in both the undifferentiated and differentiated states. This cell-based system should be useful for identifying novel hypertrophy-inducing agents as well as understanding hypertrophy signal transduction.
Cross-Doersen
Doreen
D
Research Division, Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040-9317, USA.
Isfort
Robert J
RJ
D000818:Animals; D002454:Cell Differentiation; D002999:Clone Cells; D003001:Cloning, Molecular; D006984:Hypertrophy; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000032:analysis
D011993:Recombinant Fusion Proteins; D008156:Luciferases; D018995:Myosin Heavy Chains