title: Differential ubiquitin-proteasome and autophagy signaling following rotator cuff tears and suprascapular nerve injury.
abstract: Previous studies have evaluated role of Akt/mTOR signaling in rotator cuff muscle atrophy and determined that there was differential in signaling following tendon transection (TT) and suprascapular nerve (SSN) denervation (DN), suggesting that atrophy following TT and DN was modulated by different protein degradation pathways. In this study, two muscle proteolytic systems that have been shown to be potent regulators of muscle atrophy in other injury models, the ubiquitin-proteasome pathway and autophagy, were evaluated following TT and DN. In addition to examining protein degradation, this study assessed protein synthesis rate following these two surgical models to understand how the balance between protein degradation and synthesis results in atrophy following rotator cuff injury. In contrast to the traditional theory that protein synthesis is decreased during muscle atrophy, this study suggests that protein synthesis is up-regulated in rotator cuff muscle atrophy following both surgical models. While the ubiquitin-proteasome pathway was a major contributor to the atrophy seen following DN, autophagy was a major contributor following TT. The findings of this study suggest that protein degradation is the primary factor contributing to atrophy following rotator cuff injury. However, different proteolytic pathways are activated if SSN injury is involved.
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California, 94153; Department of Orthopaedic Surgery, University of California, San Francisco, California, 94158.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D056668:Cathepsin L / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009121:Muscle Denervation; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000378:metabolism* / Q000473:pathology; D000070636:Rotator Cuff Injuries; D015398:Signal Transduction / Q000502:physiology*; D013708:Tendon Injuries / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D025801:Ubiquitin; D056668:Cathepsin L; C534280:Ctsl protein, rat; D046988:Proteasome Endopeptidase Complex
keywords: autophagy; denervation; muscle atrophy; rotator cuff tear; ubiquitin-proteasome
references.citation: Tuberc Respir Dis (Seoul). 2012 Dec;73(6):312-9
references.pmid: 23319993
references.citation: Am J Sports Med. 2007 May;35(5):719-28
references.pmid: 17337727
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):E617-24
references.pmid: 21808025
references.citation: J Cell Sci. 2012 May 15;125(Pt 10):2359-68
references.pmid: 22649254
references.citation: J Shoulder Elbow Surg. 2003 Sep-Oct;12(5):497-500
references.pmid: 14564276
references.citation: FASEB J. 2007 Jan;21(1):140-55
references.pmid: 17116744
references.citation: J Orthop Res. 2012 Dec;30(12):1963-70
references.pmid: 22696414
references.citation: PLoS One. 2012;7(12):e51238
references.pmid: 23284670
references.citation: J Shoulder Elbow Surg. 2014 Jan;23(1):99-108
references.pmid: 23790676
references.citation: J Shoulder Elbow Surg. 2001 May-Jun;10(3):199-203
references.pmid: 11408898
references.citation: J Orthop Res. 2012 Sep;30(9):1440-6
references.pmid: 22378614
references.citation: Nat Methods. 2009 Apr;6(4):275-7
references.pmid: 19305406
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5
references.pmid: 11717410
references.citation: Autophagy. 2010 Jul;6(5):600-6
references.pmid: 20431347
references.citation: J Shoulder Elbow Surg. 2003 Nov-Dec;12(6):550-4
references.pmid: 14671517
references.citation: Arch Orthop Trauma Surg. 2011 Mar;131(3):405-11
references.pmid: 20690026
references.citation: J Biol Chem. 1990 May 25;265(15):8550-7
references.pmid: 2187867
references.citation: FASEB J. 2004 Jan;18(1):39-51
references.pmid: 14718385
references.citation: Dis Model Mech. 2013 Jan;6(1):25-39
references.pmid: 23268536
references.citation: PLoS One. 2012;7(11):e50878
references.pmid: 23226416
references.citation: J Orthop Res. 2011 Apr;29(4):588-95
references.pmid: 20949443
references.citation: Autophagy. 2012 Apr;8(4):445-544
references.pmid: 22966490
references.citation: Autophagy. 2009 Feb;5(2):230-1
references.pmid: 19098460
references.citation: J Appl Physiol (1985). 2009 Aug;107(2):438-44
references.pmid: 19520837
references.citation: Mol Cell Proteomics. 2005 Sep;4(9):1370-81
references.pmid: 15965267
references.citation: Cell Metab. 2007 Dec;6(6):472-83
references.pmid: 18054316
references.citation: Biochem J. 1976 Apr 15;156(1):71-80
references.pmid: 942405
references.citation: Cell Metab. 2007 Dec;6(6):458-71
references.pmid: 18054315
references.citation: FASEB J. 2011 Mar;25(3):1028-39
references.pmid: 21148113
references.citation: J Shoulder Elbow Surg. 2006 Jul-Aug;15(4):395-8
references.pmid: 16831639
references.citation: J Cell Physiol. 2012 Apr;227(4):1569-76
references.pmid: 21678406
references.citation: Biochem J. 2001 Nov 15;360(Pt 1):143-50
references.pmid: 11696001
references.citation: J Shoulder Elbow Surg. 2008 Nov-Dec;17(6):881-5
references.pmid: 18774738
references.citation: J Bone Joint Surg Am. 2012 Apr 4;94(7):e41
references.pmid: 22488625
references.citation: Science. 2001 Nov 23;294(5547):1704-8
references.pmid: 11679633
references.citation: J Orthop Res. 2013 May;31(5):724-30
references.pmid: 23239524
references.citation: J Bone Joint Surg Am. 2006 Feb;88(2):309-16
references.pmid: 16452742
references.citation: Autophagy. 2008 Apr;4(3):378-80
references.pmid: 18227643
references.citation: Curr Opin Clin Nutr Metab Care. 2011 May;14(3):223-9
references.pmid: 21415731
references.citation: J Cell Sci. 2012 May 15;125(Pt 10):2349-58
references.pmid: 22641689
references.citation: J Biol Chem. 2013 Jan 11;288(2):1125-34
references.pmid: 23209294
references.citation: Arthroscopy. 2007 Nov;23(11):1152-61
references.pmid: 17986401
references.citation: J Biol Chem. 2012 Aug 31;287(36):30664-76
references.pmid: 22761435