Molecular mechanisms modulating muscle mass.
Skeletal muscle atrophy occurs in multiple clinical settings, including cancer, AIDS and sepsis, and is caused in part by an increase in the rate of ATP-dependent ubiquitin-mediated proteolysis. The expression of two recently identified genes encoding ubiquitin-protein ligases, MAFbx/Atrogin-1 and MuRF1, has been shown to increase during muscle atrophy. Mouse knockout studies have demonstrated that MAFbx and MuRF1 are required for muscle atrophy, and thus might be targets for clinical intervention. A second strategy for blocking atrophy involves the stimulation of pathways leading to skeletal muscle hypertrophy. Insulin-like growth factor 1 (IGF-1) is a protein growth factor that can induce skeletal muscle hypertrophy by activating the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. The pathways modulating hypertrophy and atrophy will be further discussed, to highlight potential targets for clinical intervention.
Glass
David J
DJ
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA. david.glass@regeneron.com
D005786:Gene Expression Regulation / Q000502:physiology; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I; D044767:Ubiquitin-Protein Ligases; D038362:Glycogen Synthase Kinase 3