Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy

Carberry,Steven; Brinkmeier,Heinrich; Zhang,Yaxin; Winkler,Claudia  K.; Ohlendieck,Kay

doi:10.3892/ijmm.2013.1429

Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy

Authors:
- Steven Carberry
- Heinrich Brinkmeier
- Yaxin Zhang
- Claudia K. Winkler
- Kay Ohlendieck
View Affiliations

Affiliations: Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland, Department of Pathophysiology, University of Greifswald, Greifswald, Germany
Published online on: July 3, 2013 https://doi.org/10.3892/ijmm.2013.1429
Pages: 544-556
Copyright: © Carberry et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20-25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein expression patterns in the muscle subtypes from mdx mice may be due to dissimilar downstream events, including differences in muscle structure or compensatory mechanisms that counteract pathophysiological processes. The interosseus muscle from mdx mice possibly represents a naturally protected phenotype.

View Figures

View References

1	Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J and Constantin C: Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9:77–93. 2010. View Article : Google Scholar : PubMed/NCBI
2	Dalkilic I and Kunkel LM: Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev. 13:231–238. 2003. View Article : Google Scholar : PubMed/NCBI
3	Guglieri M and Bushby K: Molecular treatments in Duchenne muscular dystrophy. Curr Opin Pharmacol. 10:331–337. 2010. View Article : Google Scholar : PubMed/NCBI
4	Mosqueira M, Zeiger U, Förderer M, Brinkmeier H and Fink RH: Cardiac and respiratory dysfunction in Duchenne muscular dystrophy and the role of second messengers. Med Res Rev. April 30–2013.(Epub ahead of print).
5	Partridge TA: Impending therapies for Duchenne muscular dystrophy. Curr Opin Neurol. 24:415–422. 2011. View Article : Google Scholar : PubMed/NCBI
6	Spurney CF, Gordish-Dressman H, Guerron AD, Sali A, Pandey GS, Rawat R, Van Der Meulen JH, Cha HJ, Pistilli EE, Partridge TA, Hoffman EP and Nagaraju K: Preclinical drug trials in the mdx mouse: assessment of reliable and sensitive outcome measures. Muscle Nerve. 39:591–602. 2009. View Article : Google Scholar : PubMed/NCBI
7	Banks GB and Chamberlain JS: The value of mammalian models for duchenne muscular dystrophy in developing therapeutic strategies. Curr Top Dev Biol. 84:431–453. 2008. View Article : Google Scholar : PubMed/NCBI
8	Durbeej M and Campbell KP: Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. Curr Opin Genet Dev. 12:349–361. 2002. View Article : Google Scholar : PubMed/NCBI
9	Tutdibi O, Brinkmeier H, Rüdel R and Föhr KJ: Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR-MDX mice is reduced by ion channel blockers. J Physiol. 515:859–868. 1999. View Article : Google Scholar : PubMed/NCBI
10	Wells DJ and Wells KE: What do animal models have to tell us regarding Duchenne muscular dystrophy? Acta Myol. 24:172–180. 2005.PubMed/NCBI
11	Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG and Barnard PJ: The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science. 244:1578–1580. 1989. View Article : Google Scholar : PubMed/NCBI
12	Dowling P, Lohan J and Ohlendieck K: Comparative analysis of Dp427-deficient mdx tissues shows that the milder dystrophic phenotype of extraocular and toe muscle fibres is associated with a persistent expression of beta-dystroglycan. Eur J Cell Biol. 82:222–230. 2003. View Article : Google Scholar
13	Marques MJ, Ferretti R, Vomero VU, Minatel E and Neto HS: Intrinsic laryngeal muscles are spared from myonecrosis in the mdx mouse model of Duchenne muscular dystrophy. Muscle Nerve. 35:349–353. 2007. View Article : Google Scholar : PubMed/NCBI
14	Porter JD, Merriam AP, Khanna S, Andrade FH, Richmonds CR, Leahy P, Cheng G, Karathanasis P, Zhou X, Kusner LL, Adams ME, Willem M, Mayer U and Kaminski HJ: Constitutive properties, not molecular adaptations, mediate extraocular muscle sparing in dystrophic mdx mice. FASEB J. 17:893–895. 2003.PubMed/NCBI
15	Carnwath JW and Shotton DM: Muscular dystrophy in the mdx mouse: histopathology of the soleus and extensor digitorum longus muscles. J Neurol Sci. 80:39–54. 1987. View Article : Google Scholar : PubMed/NCBI
16	Coulton GR, Morgan JE, Partridge TA and Sloper JC: The mdx mouse skeletal muscle myopathy: I. A histological, morphometric and biochemical investigation. Neuropathol Appl Neurobiol. 14:53–70. 1988. View Article : Google Scholar : PubMed/NCBI
17	Torres LF and Duchen LW: The mutant mdx: inherited myopathy in the mouse. Morphological studies of nerves, muscles and end-plates. Brain. 110:269–299. 1987. View Article : Google Scholar : PubMed/NCBI
18	Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT and Kelly AM: The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature. 352:536–539. 1991. View Article : Google Scholar : PubMed/NCBI
19	Dupont-Versteegden EE and McCarter RJ: Differential expression of muscular dystrophy in diaphragm versus hindlimb muscles of mdx mice. Muscle Nerve. 15:1105–1110. 1992. View Article : Google Scholar : PubMed/NCBI
20	Lynch GS, Rafael JA, Hinkle RT, Cole NM, Chamberlain JS and Faulkner JA: Contractile properties of diaphragm muscle segments from old mdx and old transgenic mdx mice. Am J Physiol. 272:C2063–C2068. 1997.PubMed/NCBI
21	Ohlendieck K: Proteomics of skeletal muscle differentiation, neuromuscular disorders and fiber aging. Expert Rev Proteomics. 7:283–296. 2010. View Article : Google Scholar : PubMed/NCBI
22	Gelfi C, Vasso M and Cerretelli P: Diversity of human skeletal muscle in health and disease: contribution of proteomics. J Proteomics. 74:774–795. 2011. View Article : Google Scholar : PubMed/NCBI
23	Ohlendieck K: Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques. Skelet Muscle. 1:62011. View Article : Google Scholar : PubMed/NCBI
24	Ohlendieck K: Proteomic identification of biomarkers of skeletal muscle disorders. Biomark Med. 7:169–186. 2013. View Article : Google Scholar : PubMed/NCBI
25	Lewis C, Carberry S and Ohlendieck K: Proteomic profiling of x-linked muscular dystrophy. J Muscle Res Cell Motil. 30:267–269. 2009. View Article : Google Scholar : PubMed/NCBI
26	Ge Y, Molloy MP, Chamberlain JS and Andrews PC: Proteomic analysis of mdx skeletal muscle: great reduction of adenylate kinase 1 expression and enzymatic activity. Proteomics. 3:1895–1903. 2003. View Article : Google Scholar : PubMed/NCBI
27	Ge Y, Molloy MP, Chamberlain JS and Andrews PC: Differential expression of the skeletal muscle proteome in mdx mice at different ages. Electrophoresis. 25:2576–2585. 2004. View Article : Google Scholar : PubMed/NCBI
28	Doran P, Dowling P, Lohan J, McDonnell K, Poetsch S and Ohlendieck K: Subproteomics analysis of Ca⁺-binding proteins demonstrates decreased calsequestrin expression in dystrophic mouse skeletal muscle. Eur J Biochem. 271:3943–3952. 2004.
29	Doran P, Dowling P, Donoghue P, Buffini M and Ohlendieck K: Reduced expression of regucalcin in young and aged mdx diaphragm indicates abnormal cytosolic calcium handling in dystrophin-deficient muscle. Biochim Biophys Acta. 1764:773–785. 2006. View Article : Google Scholar : PubMed/NCBI
30	Doran P, Martin G, Dowling P, Jockusch H and Ohlendieck K: Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP. Proteomics. 6:4610–4621. 2006. View Article : Google Scholar : PubMed/NCBI
31	Doran P, Wilton SD, Fletcher S and Ohlendieck K: Proteomic profiling of antisense-induced exon skipping reveals reversal of pathobiochemical abnormalities in dystrophic mdx diaphragm. Proteomics. 9:671–685. 2009. View Article : Google Scholar : PubMed/NCBI
32	Gardan-Salmon D, Dixon JM, Lonergan SM and Selsby JT: Proteomic assessment of the acute phase of dystrophin deficiency in mdx mice. Eur J Appl Physiol. 111:2763–2773. 2011. View Article : Google Scholar : PubMed/NCBI
33	Carberry S, Zweyer M, Swandulla D and Ohlendieck K: Proteomics reveals drastic increase of extracellular matrix proteins collagen and dermatopontin in the aged mdx diaphragm model of Duchenne muscular dystrophy. Int J Mol Med. 30:229–234. 2012.
34	Carberry S, Zweyer M, Swandulla D and Ohlendieck K: Profiling of age-related changes in the tibialis anterior muscle proteome of the mdx mouse model of dystrophinopathy. J Biomed Biotechnol. 2012:6916412012. View Article : Google Scholar : PubMed/NCBI
35	Lewis C and Ohlendieck K: Proteomic profiling of naturally protected extraocular muscles from the dystrophin-deficient mdx mouse. Biochem Biophys Res Commun. 396:1024–1029. 2010. View Article : Google Scholar : PubMed/NCBI
36	Rayavarapu S, Coley W, Cakir E, Jahnke V, Takeda S, Aoki Y, Gordish-Dressman H, Jaiswal JK, Hoffman EP, Brown KJ, Hathout Y and Nagaraju K: Identification of disease specific pathways using in vivo SILAC proteomics in dystrophin deficient mdx mouse. Mol Cell Proteomics. 12:1061–1073. 2013. View Article : Google Scholar : PubMed/NCBI
37	Alagaratnam S, Mertens BJ, Dalebout JC, Deelder AM, van Ommen GJ, den Dunnen JT and ‘t Hoen PA: Serum protein profiling in mice: identification of Factor XIIIa as a potential biomarker for muscular dystrophy. Proteomics. 8:1552–1563. 2008. View Article : Google Scholar : PubMed/NCBI
38	Colussi C, Banfi C, Brioschi M, Tremoli E, Straino S, Spallotta F, Mai A, Rotili D, Capogrossi MC and Gaetano C: Proteomic profile of differentially expressed plasma proteins from dystrophic mice and following suberoylanilide hydroxamic acid treatment. Proteomics Clin Appl. 4:71–83. 2010. View Article : Google Scholar
39	Gulston MK, Rubtsov DV, Atherton HJ, Clarke K, Davies KE, Lilley KS and Griffin JL: A combined metabolomic and proteomic investigation of the effects of a failure to express dystrophin in the mouse heart. J Proteome Res. 7:2069–2077. 2008. View Article : Google Scholar : PubMed/NCBI
40	Johnson EK, Zhang L, Adams ME, Phillips A, Freitas MA, Froehner SC, Green-Church KB and Montanaro F: Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins. PLoS One. 7:e435152012. View Article : Google Scholar : PubMed/NCBI
41	Lewis C, Jockusch H and Ohlendieck K: Proteomic profiling of the Dystrophin-deficient MDX heart reveals drastically altered levels of key metabolic and contractile proteins. J Biomed Biotechnol. 2010:6485012010. View Article : Google Scholar : PubMed/NCBI
42	Holland A, Dowling P, Zweyer M, Swandulla D, Henry M, Clynes M and Ohlendieck K: Proteomic profiling of cardiomyopathic tissue from the aged mdx model of Duchenne muscular dystrophy reveals a drastic decrease in laminin, nidogen and annexin. Proteomics. May 23–2013.(Epub ahead of print).
43	Jarmey C: The Atlas of Musculo-skeletal Anatomy. Lotus Publishing; Chichester: 2004
44	Lieber RL: Skeletal muscle Structure, Function, and Plasticity. 3rd edition. Lippincott Williams & Wilkins; Baltimore, MD: 2009
45	Stal P, Eriksson PO, Eriksson A and Thornell LE: Enzyme-histochemical differences in fibre-type between the human major and minor zygomatic and the first dorsal interosseus muscles. Arch Oral Biol. 32:833–841. 1987. View Article : Google Scholar
46	Staron RS: Human skeletal muscle fiber types: delineation, development, and distribution. Can J Appl Physiol. 22:307–327. 1997. View Article : Google Scholar : PubMed/NCBI
47	Mallouk N, Jacquemond V and Allard B: Elevated subsarcolemmal Ca²⁺in mdx mouse skeletal muscle fibers detected with Ca²⁺-activated K⁺channels. Proc Natl Acad Sci USA. 97:4950–4955. 2000.
48	Pritschow BW, Lange T, Kasch J, Kunert-Keil C, Liedtke W and Brinkmeier H: Functional TRPV4 channels are expressed in mouse skeletal muscle and can modulate resting Ca²⁺influx and muscle fatigue. Pflügers Arch. 461:115–122. 2011.PubMed/NCBI
49	Boittin FX, Shapovalov G, Hirn C and Rüegg UT: Phospholipase A2-derived lysophosphatidylcholine triggers Ca²⁺entry in dystrophic skeletal muscle fibers. Biochem Biophys Res Commun. 391:401–406. 2010. View Article : Google Scholar : PubMed/NCBI
50	Teichmann MD, Wegner FV, Fink RH, Chamberlain JS, Launikonis BS, Martinac B and Friedrich O: Inhibitory control over Ca²⁺ sparks via mechanosensitive channels is disrupted in dystrophin deficient muscle but restored by mini-dystrophin expression. PLoS One. 3:e36442008.PubMed/NCBI
51	Ohlendieck K and Campbell KP: Dystrophin-associated proteins are greatly reduced in skeletal muscle from mdx mice. J Cell Biol. 115:1685–1694. 1991. View Article : Google Scholar : PubMed/NCBI
52	Krüger J, Kunert-Keil C, Bisping F and Brinkmeier H: Transient receptor potential cation channels in normal and dystrophic mdx muscle. Neuromuscul Disord. 18:501–513. 2008.PubMed/NCBI
53	Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI
54	Gannon J, Staunton L, O’Connell K, Doran P and Ohlendieck K: Phosphoproteomic analysis of aged skeletal muscle. Int J Mol Med. 22:33–42. 2008.
55	Rabilloud T, Strub JM, Luche S, van Dorsselaer A and Lunardi J: A comparison between Sypro Ruby and ruthenium II tris (bathophenanthroline disulfonate) as fluorescent stains for protein detection in gels. Proteomics. 1:699–704. 2001. View Article : Google Scholar : PubMed/NCBI
56	Lewis C and Ohlendieck K: Mass spectrometric identification of dystrophin isoform Dp427 by on-membrane digestion of sarcolemma from skeletal muscle. Anal Biochem. 404:197–203. 2010. View Article : Google Scholar : PubMed/NCBI
57	Donoghue P, Doran P, Wynne K, Pedersen K, Dunn MJ and Ohlendieck K: Proteomic profiling of chronic low-frequency stimulated fast muscle. Proteomics. 7:3417–3430. 2007. View Article : Google Scholar : PubMed/NCBI
58	Staunton L, Jockusch H, Wiegand C, Albrecht T and Ohlendieck K: Identification of secondary effects of hyperexcitability by proteomic profiling of myotonic mouse muscle. Mol Biosyst. 7:2480–2489. 2011. View Article : Google Scholar : PubMed/NCBI
59	Kornegay JN, Childers MK, Bogan DJ, Bogan JR, Nghiem P, Wang J, Fan Z, Howard JF Jr, Schatzberg SJ, Dow JL, Grange RW, Styner MA, Hoffman EP and Wagner KR: The paradox of muscle hypertrophy in muscular dystrophy. Phys Med Rehabil Clin N Am. 23:149–172. 2012. View Article : Google Scholar : PubMed/NCBI
60	Andres-Mateos E, Brinkmeier H, Burks TN, Mejias R, Files DC, Steinberger M, Soleimani A, Marx R, Simmers JL, Lin B, Finanger Hedderick E, Marr TG, Lin BM, Hourde C, Leinwand LA, Kuhl D, Foller M, Vogelsang S, Hernandez-Diaz I, Vaughan DK, Alvarez de la Rosa D, Lang F and Cohn RD: Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy. EMBO Mol Med. 5:80–91. 2013. View Article : Google Scholar : PubMed/NCBI
61	Gundersen K: Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise. Biol Rev Camb Philos Soc. 86:564–600. 2011. View Article : Google Scholar : PubMed/NCBI
62	Zeiger U, Mitchell CH and Khurana TS: Superior calcium homeostasis of extraocular muscles. Exp Eye Res. 91:613–622. 2010. View Article : Google Scholar : PubMed/NCBI
63	Swartz DR, Yang Z, Sen A, Tikunova SB and Davis JP: Myofibrillar troponin exists in three states and there is signal transduction along skeletal myofibrillar thin filaments. J Mol Biol. 361:420–435. 2006. View Article : Google Scholar
64	Gordon AM, Homsher E and Regnier M: Regulation of contraction in striated muscle. Physiol Rev. 80:853–924. 2000.PubMed/NCBI
65	Gonzalez B, Negredo P, Hernando R and Manso R: Protein variants of skeletal muscle regulatory myosin light chain isoforms: prevalence in mammals, generation and transitions during muscle remodelling. Pflügers Arch. 443:377–386. 2002.
66	Bozzo C, Spolaore B, Toniolo L, Stevens L, Bastide B, Cieniewski-Bernard C, Fontana A, Mounier Y and Reggiani C: Nerve influence on myosin light chain phosphorylation in slow and fast skeletal muscles. FEBS J. 272:5771–5785. 2005. View Article : Google Scholar : PubMed/NCBI
67	Clark KA, McElhinny AS, Beckerle MC and Gregorio CC: Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol. 18:637–706. 2002. View Article : Google Scholar : PubMed/NCBI
68	Pette D and Staron RS: Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech. 50:500–509. 2000. View Article : Google Scholar : PubMed/NCBI
69	Holland A and Ohlendieck K: Proteomic profiling of the contractile apparatus from skeletal muscle. Expert Rev Proteomics. (In press).
70	Donoghue P, Doran P, Dowling P and Ohlendieck K: Differential expression of the fast skeletal muscle proteome following chronic low-frequency stimulation. Biochim Biophys Acta. 1752:166–176. 2005. View Article : Google Scholar : PubMed/NCBI
71	Philippova M, Banfi A, Ivanov D, Gianni-Barrera R, Allenspach R, Erne P and Resink T: Atypical GPI-anchored T-cadherin stimulates angiogenesis in vitro and in vivo. Arterioscler Thromb Vasc Biol. 26:2222–2230. 2006. View Article : Google Scholar : PubMed/NCBI
72	Steinacker P, Aitken A and Otto M: 14-3-3 proteins in neurodegeneration. Semin Cell Dev Biol. 22:696–704. 2011. View Article : Google Scholar
73	Ohlendieck K: Proteomics of skeletal muscle glycolysis. Biochim Biophys Acta. 1804:2089–2101. 2010. View Article : Google Scholar : PubMed/NCBI
74	Gelfi C, Vigano A, De Palma S, Ripamonti M, Begum S, Cerretelli P and Wait R: 2-D protein maps of rat gastrocnemius and soleus muscles: a tool for muscle plasticity assessment. Proteomics. 6:321–340. 2006. View Article : Google Scholar : PubMed/NCBI
75	Wells GD, Selvadurai H and Tein I: Bioenergetic provision of energy for muscular activity. Paediatr Respir Rev. 10:83–90. 2009. View Article : Google Scholar : PubMed/NCBI
76	Rakus D, Pasek M, Krotkiewski H and Dzugaj A: Interaction between muscle aldolase and muscle fructose 1,6-bisphosphatase results in the substrate channeling. Biochemistry. 43:14948149572004. View Article : Google Scholar : PubMed/NCBI
77	Kim JW and Dang CV: Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 30:142–150. 2005. View Article : Google Scholar : PubMed/NCBI