title: Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model.
abstract: Atrophy of the rotator cuff muscles is a factor that complicates the treatment of a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern the development of muscle atrophy after RCTs have not been well defined. The Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in maintaining muscle mass in response to mechanical loading. The role of this pathway in the development of muscle atrophy after a massive RCT remains unknown. The purpose of this study was to investigate the regulation of the Akt/mTOR pathway in the development of muscle atrophy after a RCT and suprascapular nerve (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how this pathway interacts with two atrophy-related genes, MuRF-1 and MAFbx, in supraspinatus muscles of rats that underwent unilateral complete rotator cuff tendon transection or SSN transection. Akt/mTOR activity was significantly reduced after tendon rupture, but increased after nerve injury. MuRF-1 and MAFbx were only up-regulated following denervation. These results suggest that tendon transection leads to a decrease in protein synthesis with down-regulation of the Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein degradation via up-regulation of expression of MuRF-1 and MAFbx.
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, Califronia, USA.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Sanjum P
authors.initials: SP
authors.lastname: Samagh
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Dang
authors.forename: Dominique
authors.initials: D
authors.lastname: Laron
authors.forename: David H
authors.initials: DH
authors.lastname: Lovett
authors.forename: Sue C
authors.initials: SC
authors.lastname: Bodine
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
mesh_terms: D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000070636:Rotator Cuff Injuries; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013708:Tendon Injuries / Q000150:complications* / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases