title: Altered gene expression patterns in muscle ring finger 1 null mice during denervation- and dexamethasone-induced muscle atrophy.
abstract: Muscle atrophy can result from inactivity or unloading on one hand or the induction of a catabolic state on the other. Muscle-specific ring finger 1 (MuRF1), a member of the tripartite motif family of E3 ubiquitin ligases, is an essential mediator of multiple conditions inducing muscle atrophy. While most studies have focused on the role of MuRF1 in protein degradation, the protein may have other roles in regulating skeletal muscle mass and metabolism. We therefore systematically evaluated the effect of MuRF1 on gene expression during denervation and dexamethasone-induced atrophy. We find that the lack of MuRF1 leads to few differences in control animals, but there were several significant differences in specific sets of genes upon denervation- and dexamethasone-induced atrophy. For example, during denervation, MuRF1 knockout mice showed delayed repression of metabolic and structural genes and blunted induction of genes associated with the neuromuscular junction. In the latter case, this pattern correlates with blunted HDAC4 and myogenin upregulation. Lack of MuRF1 caused fewer changes in the dexamethasone-induced atrophy program, but certain genes involved in fat metabolism and intracellular signaling were affected. Our results demonstrate a new role for MuRF1 in influencing gene expression in two important models of muscle atrophy.
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors.forename: J David
authors.initials: JD
authors.lastname: Furlow
authors.forename: Monica L
authors.initials: ML
authors.lastname: Watson
authors.forename: David S
authors.initials: DS
authors.lastname: Waddell
authors.forename: Eric S
authors.initials: ES
authors.lastname: Neff
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Baehr
authors.forename: Adam P
authors.initials: AP
authors.lastname: Ross
authors.forename: Sue C
authors.initials: SC
authors.lastname: Bodine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D003714:Denervation / Q000662:veterinary*; D003907:Dexamethasone / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D003907:Dexamethasone; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: denervation; gene expression; glucocorticoid; microarray; skeletal muscle