title: Loss of REDD1 augments the rate of the overload-induced increase in muscle mass.
abstract: The overload-induced increase in muscle mass is accompanied by protein accretion; however, the initiating events are poorly understood. Regulated in Development and DNA Damage 1 (REDD1), a repressor of the mechanistic target of rapamycin in complex 1 (mTORC1), blunts the elevation in protein synthesis induced by acute muscle contractions. Therefore, this study was designed to determine whether REDD1 alters the rate of the overload-induced increase in muscle mass. Wild-type (WT) and REDD1-null mice underwent unilateral functional overload (OV) of the plantaris, while the contralateral sham leg served as a control. After 3 and 5 days of OV, puromycin incorporation was used as a measurement of protein synthesis. The percent increase in plantaris wet weight and protein content was greater in REDD1-null mice after 3, 5, and 10 days OV. The overload-stimulated rate of protein synthesis in the plantaris was similar between genotypes after 3 days OV, but translational capacity was lower in REDD1-null mice, indicating elevated translational efficiency. This was likely due to elevated absolute mTORC1 signaling [phosphorylation of p70S6K1 (Thr-389) and 4E-BP1 (Ser-65)]. By 5 days of OV, the rate of protein synthesis in REDD1-null mice was lower than WT mice with no difference in absolute mTORC1 signaling. Additionally, markers of autophagy (LC3II/I ratio and p62 protein) were decreased to a greater absolute extent after 3 days OV in REDD1-null mice. These data suggest that loss of REDD1 augments the rate of the OV-induced increase in muscle mass by altering multiple protein balance pathways.
authors.affiliation: Institute of Exercise Physiology and Wellness, The University of Central Florida, Orlando, Florida; bradley.gordon@ucf.edu.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Gordon
authors.affiliation: Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania; and.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steiner
authors.affiliation: Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania; and.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nader
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Jefferson
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Scot R
authors.initials: SR
authors.lastname: Kimball
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology*; D009929:Organ Size / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C469992:Ddit4 protein, mouse; D009124:Muscle Proteins; D014157:Transcription Factors
keywords: autophagy; protein synthesis; resistance exercise; ribosome biogenesis