title: Effect of postdevelopmental myostatin depletion on myofibrillar protein metabolism.
abstract: It is unclear whether the muscle hypertrophy induced by loss of myostatin signaling in mature muscles is maintained only by increased protein synthesis or whether reduced proteolysis contributes. To address this issue, we depleted myostatin by activating Cre recombinase for 2 wk in mature mice in which Mstn exon 3 was flanked by loxP sequences. The rate of phenylalanine tracer incorporation into myofibrillar proteins was determined 2, 5, and 24 wk after Cre activation ended. At all of these time points, myostatin-deficient mice had increased gastrocnemius and quadriceps muscle mass (≥27%) and increased myofibrillar synthesis rate per gastrocnemius muscle (≥19%) but normal myofibrillar synthesis rates per myofibrillar mass or RNA mass. Mean fractional myofibrillar degradation rates (estimated from the difference between rate of synthesis and rate of change in myofibrillar mass) and muscle concentrations of free 3-methylhistidine (from actin and myosin degradation) were unaffected by myostatin knockout. Overnight food deprivation reduced myofibrillar synthesis and ribosomal protein S6 phosphorylation and increased concentrations of 3-methylhistidine, muscle RING finger-1 mRNA, and atrogin-1 mRNA. Myostatin depletion did not affect these responses to food deprivation. These data indicate that maintenance of the muscle hypertrophy caused by loss of myostatin is mediated by increased protein synthesis per muscle fiber rather than suppression of proteolysis.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Rochester, Rochester, NY 14642, USA. stephen_welle@urmc.rochester.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Welle
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.forename: Kerri
authors.initials: K
authors.lastname: Burgess
mesh_terms: D000818:Animals; D005508:Food Deprivation / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008762:Methylhistidines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism*; D055435:Myostatin / Q000172:deficiency* / Q000502:physiology*; D010766:Phosphorylation; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D008762:Methylhistidines; D009124:Muscle Proteins; D055435:Myostatin; D038601:Ribosomal Protein S6; D000070584:Tripartite Motif Proteins; D012313:RNA; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; C028118:3-methylhistidine