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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2011

Open Access 01-12-2011 | Research article

Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology

Authors: Parco M Siu, Bee T Teng, Xiao M Pei, Eric W Tam

Published in: BMC Musculoskeletal Disorders | Issue 1/2011

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Abstract

Background

The molecular mechanism initiating deep pressure ulcer remains to be elucidated. The present study tested the hypothesis that the ubiquitin proteasome system is involved in the signalling mechanism in pressure-induced deep tissue injury.

Methods

Adult Sprague Dawley rats were subjected to an experimental compression model to induce deep tissue injury. The tibialis region of the right hind limb was subjected to 100 mmHg of static pressure for six hours on each of two consecutive days. The compression pressure was continuously monitored by a three-axial force transducer within the compression indentor. The left hind limb served as the intra-animal control. Muscle tissues underneath the compressed region were collected and used for analyses.

Results

Our results demonstrated that the activity of 20S proteasome and the protein abundance of ubiquitin and MAFbx/atrogin-1 were elevated in conjunction with pathohistological changes in the compressed muscle, as compared to control muscle. The administration of the proteasome inhibitor MG132 was found to be effective in ameliorating the development of pathological histology in compressed muscle. Furthermore, 20S proteasome activity and protein content of ubiquitin and MAFbx/atrogin-1 showed no apparent increase in the MG132-treated muscle following compression.

Conclusion

Our data suggest that the ubiquitin proteasome system may play a role in the pathogenesis of pressure-induced deep tissue injury.
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Literature
1.
Garcia AD, Thomas DR: Assessment and management of chronic pressure ulcers in the elderly. Med Clin North Am. 2006, 90: 925-944. 10.1016/j.mcna.2006.05.018.CrossRefPubMed
2.
Cullum N, McInnes E, Bell-Syer SE, Legood R: Support surfaces for pressure ulcer prevention. Cochrane Database Syst Rev. 2004, CD001735-
3.
Gawlitta D, Li W, Oomens CW, Baaijens FP, Bader DL, Bouten CV: The relative contributions of compression and hypoxia to development of muscle tissue damage: an in vitro study. Ann Biomed Eng. 2007, 35: 273-284. 10.1007/s10439-006-9222-5.CrossRefPubMed
4.
Ankrom MA, Bennett RG, Sprigle S, Langemo D, Black JM, Berlowitz DR, Lyder CH: Pressure-related deep tissue injury under intact skin and the current pressure ulcer staging systems. Adv Skin Wound Care. 2005, 18: 35-42. 10.1097/00129334-200501000-00016.CrossRefPubMed
5.
Black J, Baharestani M, Cuddigan J, Dorner B, Edsberg L, Langemo D, Posthauer ME, Ratliff C, Taler G: National Pressure Ulcer Advisory Panel's updated pressure ulcer staging system. Urol Nurs. 2007, 27: 144-50. 156PubMed
6.
Donnelly J: Should we include deep tissue injury in pressure ulcer staging systems? The NPUAP debate. J Wound Care. 2005, 14: 207-210.CrossRefPubMed
7.
Gefen A: Bioengineering models of deep tissue injury. Adv Skin Wound Care. 2008, 21: 30-36. 10.1097/01.ASW.0000305403.89737.6c.CrossRefPubMed
8.
Fleck CA: Suspected deep tissue injury. Adv Skin Wound Care. 2007, 20: 413-415. 10.1097/01.ASW.0000280206.96378.5b.CrossRefPubMed
9.
Gefen A: Risk factors for a pressure-related deep tissue injury: a theoretical model. Med Biol Eng Comput. 2007, 45: 563-573. 10.1007/s11517-007-0187-9.CrossRefPubMed
10.
Arnason T, Ellison MJ: Stress resistance in Saccharomyces cerevisiae is strongly correlated with assembly of a novel type of multiubiquitin chain. Mol Cell Biol. 1994, 14: 7876-7883.CrossRefPubMedPubMedCentral
11.
Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ: Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000, 103: 351-361. 10.1016/S0092-8674(00)00126-4.CrossRefPubMed
12.
Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM: De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004, 430: 694-699. 10.1038/nature02794.CrossRefPubMed
13.
Glickman MH, Ciechanover A: The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002, 82: 373-428.CrossRefPubMed
14.
Taillandier D, Combaret L, Pouch MN, Samuels SE, Bechet D, Attaix D: The role of ubiquitin-proteasome-dependent proteolysis in the remodelling of skeletal muscle. Proc Nutr Soc. 2004, 63: 357-361. 10.1079/PAR2004358.CrossRefPubMed
15.
Zhang P, Chen X, Fan M: Signaling mechanisms involved in disuse muscle atrophy. Med Hypotheses. 2007, 69: 310-321. 10.1016/j.mehy.2006.11.043.CrossRefPubMed
16.
Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ: Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001, 294: 1704-1708. 10.1126/science.1065874.CrossRefPubMed
17.
Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL: Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA. 2001, 98: 14440-14445. 10.1073/pnas.251541198.CrossRefPubMedPubMedCentral
18.
Franch HA, Price SR: Molecular signaling pathways regulating muscle proteolysis during atrophy. Curr Opin Clin Nutr Metab Care. 2005, 8: 271-275. 10.1097/01.mco.0000165005.01331.45.CrossRefPubMed
19.
Miyazaki M, Noguchi M, Takemasa T: Intermittent reloading attenuates muscle atrophy through modulating Akt/mTOR pathway. Med Sci Sports Exerc. 2008, 40: 848-855. 10.1249/MSS.0b013e318163275f.CrossRefPubMed
20.
de Palma L, Marinelli M, Pavan M, Orazi A: Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine. 2008, 75: 53-57. 10.1016/j.jbspin.2007.04.019.CrossRefPubMed
21.
Edlich RF, Winters KL, Woodard CR, Buschbacher RM, Long WB, Gebhart JH, Ma EK: Pressure ulcer prevention. J Long Term Eff Med Implants. 2004, 14: 285-304. 10.1615/JLongTermEffMedImplants.v14.i4.20.CrossRefPubMed
22.
Struck BD, Wright JE: Pressure ulcers and endothelial dysfunction: is there a link?. J Nutr Elder. 2007, 26: 105-117. 10.1300/J052v26n03_05.CrossRefPubMed
23.
Bouten CV, Oomens CW, Baaijens FP, Bader DL: The etiology of pressure ulcers: skin deep or muscle bound?. Arch Phys Med Rehabil. 2003, 84: 616-619. 10.1053/apmr.2003.50038.CrossRefPubMed
24.
Daniel RK, Priest DL, Wheatley DC: Etiologic factors in pressure sores: an experimental model. Arch Phys Med Rehabil. 1981, 62: 492-498.PubMed
25.
Nola GT, Vistnes LM: Differential response of skin and muscle in the experimental production of pressure sores. Plast Reconstr Surg. 1980, 66: 728-733. 10.1097/00006534-198011000-00008.CrossRefPubMed
26.
Salcido R, Donofrio JC, Fisher SB, LeGrand EK, Dickey K, Carney JM, Schosser R, Liang R: Histopathology of pressure ulcers as a result of sequential computer-controlled pressure sessions in a fuzzy rat model. Adv Wound Care. 1994, 7: 23-4. 26, 28PubMed
27.
Attaix D, Ventadour S, Codran A, Bechet D, Taillandier D, Combaret L: The ubiquitin-proteasome system and skeletal muscle wasting. Essays Biochem. 2005, 41: 173-186. 10.1042/EB0410173.CrossRefPubMed
28.
Cao PR, Kim HJ, Lecker SH: Ubiquitin-protein ligases in muscle wasting. Int J Biochem Cell Biol. 2005, 37: 2088-2097. 10.1016/j.biocel.2004.11.010.CrossRefPubMed
29.
Kwan MP, Tam EW, Lo SC, Leung MC, Lau RY: The time effect of pressure on tissue viability: investigation using an experimental rat model. Exp Biol Med (Maywood). 2007, 232: 481-487.
30.
Siu PM, Tam EW, Teng BT, Pei XM, Ng JW, Benzie IF, Mak AF: Muscle apoptosis is induced in pressure-induced deep tissue injury. J Appl Physiol. 2009, 107: 1266-1275. 10.1152/japplphysiol.90897.2008.CrossRefPubMed
31.
Teng BT, Pei XM, Tam EW, Benzie IF, Siu PM: Opposing responses of apoptosis and autophagy to moderate compression in skeletal muscle. Acta Physiol (Oxf). 2010, 201: 239-254. 10.1111/j.1748-1716.2010.02173.x.CrossRef
32.
Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL: Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994, 78: 761-771. 10.1016/S0092-8674(94)90462-6.CrossRefPubMed
33.
Chen X, Li SL, Wu T, Liu JD: Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats. World J Gastroenterol. 2008, 14: 3249-3253. 10.3748/wjg.14.3249.CrossRefPubMedPubMedCentral
34.
Yuan B, Xing Y, Horst RL, Drezner MK: Evidence for abnormal translational regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase activity in the hyp-mouse. Endocrinology. 2004, 145: 3804-3812. 10.1210/en.2004-0192.CrossRefPubMed
35.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
36.
Mitch WE, Goldberg AL: Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med. 1996, 335: 1897-1905. 10.1056/NEJM199612193352507.CrossRefPubMed
37.
Granado M, Martin AI, Priego T, Lopez-Calderon A, Villanua MA: Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats. J Endocrinol. 2006, 191: 319-326. 10.1677/joe.1.06931.CrossRefPubMed
38.
Nedergaard A, Vissing K, Overgaard K, Kjaer M, Schjerling P: Expression patterns of atrogenic and ubiquitin proteasome component genes with exercise: effect of different loading patterns and repeated exercise bouts. J Appl Physiol. 2007, 103: 1513-1522. 10.1152/japplphysiol.01445.2006.CrossRefPubMed
39.
Witt CC, Witt SH, Lerche S, Labeit D, Back W, Labeit S: Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J. 2008, 27: 350-360. 10.1038/sj.emboj.7601952.CrossRefPubMed
40.
Drummond MJ, Glynn EL, Lujan HL, Dicarlo SE, Rasmussen BB: Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle. Muscle Nerve. 2008, 37: 505-513. 10.1002/mus.20976.CrossRefPubMedPubMedCentral
41.
Koyama S, Hata S, Witt CC, Ono Y, Lerche S, Ojima K, Chiba T, Doi N, Kitamura F, Tanaka K, Abe K, Witt SH, Rybin V, Gasch A, Franz T, Labeit S, Sorimachi H: Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis. J Mol Biol. 2008, 376: 1224-1236. 10.1016/j.jmb.2007.11.049.CrossRefPubMed
42.
Lang CH, Huber D, Frost RA: Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I. Am J Physiol Regul Integr Comp Physiol. 2007, 292: R328-R336.CrossRefPubMed
43.
Vary TC, Frost RA, Lang CH: Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2008, 294: R1777-R1789.CrossRefPubMedPubMedCentral
44.
Dehoux MJ, van Beneden RP, Fernandez-Celemin L, Lause PL, Thissen JP: Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett. 2003, 544: 214-217. 10.1016/S0014-5793(03)00505-2.CrossRefPubMed
45.
Bonuccelli G, Sotgia F, Schubert W, Park DS, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, Lisanti MP: Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am J Pathol. 2003, 163: 1663-1675. 10.1016/S0002-9440(10)63523-7.CrossRefPubMedPubMedCentral
46.
Assereto S, Stringara S, Sotgia F, Bonuccelli G, Broccolini A, Pedemonte M, Traverso M, Biancheri R, Zara F, Bruno C, Lisanti MP, Minetti C: Pharmacological rescue of the dystrophin-glycoprotein complex in Duchenne and Becker skeletal muscle explants by proteasome inhibitor treatment. Am J Physiol Cell Physiol. 2006, 290: C577-C582. 10.1152/ajpcell.00434.2005.CrossRefPubMed
47.
Luo H, Wu Y, Qi S, Wan X, Chen H, Wu J: A proteasome inhibitor effectively prevents mouse heart allograft rejection. Transplantation. 2001, 72: 196-202. 10.1097/00007890-200107270-00005.CrossRefPubMed
48.
Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM: Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci USA. 1999, 96: 10403-10408. 10.1073/pnas.96.18.10403.CrossRefPubMedPubMedCentral
49.
Petrovic J, Hall H, Mehr R, Glas R, Hoglund P: Inhibition of the proteasome reduces transfer-induced diabetes in nonobese diabetic mice. Scand J Immunol. 2004, 60: 134-142. 10.1111/j.0300-9475.2004.01473.x.CrossRefPubMed
50.
Wang X, Luo H, Chen H, Duguid W, Wu J: Role of proteasomes in T cell activation and proliferation. J Immunol. 1998, 160: 788-801.PubMed
51.
Zollner TM, Podda M, Pien C, Elliott PJ, Kaufmann R, Boehncke WH: Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model. J Clin Invest. 2002, 109: 671-679.CrossRefPubMedPubMedCentral
52.
Wojcik C: Regulation of apoptosis by the ubiquitin and proteasome pathway. J Cell Mol Med. 2002, 6: 25-48. 10.1111/j.1582-4934.2002.tb00309.x.CrossRefPubMed
53.
Drexler HC: Programmed cell death and the proteasome. Apoptosis. 1998, 3: 1-7. 10.1023/A:1009604900979.CrossRefPubMed
54.
Orlowski RZ: The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ. 1999, 6: 303-313. 10.1038/sj.cdd.4400505.CrossRefPubMed
55.
Bosboom EM, Bouten CV, Oomens CW, van Straaten HW, Baaijens FP, Kuipers H: Quantification and localisation of damage in rat muscles after controlled loading; a new approach to study the aetiology of pressure sores. Med Eng Phys. 2001, 23: 195-200. 10.1016/S1350-4533(01)00034-0.CrossRefPubMed
56.
Stekelenburg A, Oomens CW, Strijkers GJ, Nicolay K, Bader DL: Compression-induced deep tissue injury examined with magnetic resonance imaging and histology. J Appl Physiol. 2006, 100: 1946-1954. 10.1152/japplphysiol.00889.2005.CrossRefPubMed
Metadata
Title
Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology
Authors
Parco M Siu
Bee T Teng
Xiao M Pei
Eric W Tam
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2011
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-12-58

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