Doran, Philip and Martin, Geraldine and Dowling, Paul and Jockusch, Harald and Ohlendieck, Kay (2006) Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP. Proteomics, 6 (16). pp. 4610-4621. ISSN 1615-9853

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Abstract

Duchenne muscular dystrophy is the most commonly inherited neuromuscular disorder in humans. Although the primary genetic deficiency of dystrophin in X-linkedmuscular dystrophy is established, it isnotwell-known howpathophysiological events trigger the actual fibre degeneration. We have therefore performed a DIGE analysis of normal diaphragm muscle versus the severely affected x-linked muscular dystrophy (MDX) diaphragm, which represents an established animal model of dystrophinopathy. Out of 2398 detectable 2-D protein spots, 35 proteins showed a drastic differential expression pattern, with 21 proteins being decreased, including Fbxo11-protein, adenylate kinase, b-haemoglobin and dihydrolipoamide dehydrogenase, and 14 proteins being increased, including cvHSP, aldehyde reductase, desmin, vimentin, chaperonin, cardiac and muscle myosin heavy chain. This suggests that lack of sarcolemmal integrity triggers a generally perturbed protein expression pattern in dystrophin-deficient fibres. However, the most significant finding was the dramatic increase in the small heat shock protein cvHSP, which was confirmed by 2-D immunoblotting. Confocal fluorescence microscopy revealed elevated levels of cvHSP in MDX fibres. An immunoblotting survey of other key heat shock proteins showed a differential expression pattern in MDX diaphragm. Stress response appears to be an important cellular mechanism in dystrophic muscle andmay be exploitable as a new approach to counteractmuscle degeneration.

Item Type:	Article
Keywords:	Cardiovascular heat shock protein; DIGE; MDX diaphragm; Muscular dystrophy; Skeletal muscle proteomics;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7349
Identification Number:	https://doi.org/10.1002/pmic.200600082
Depositing User:	Paul Dowling
Date Deposited:	16 Aug 2016 15:45
Journal or Publication Title:	Proteomics
Publisher:	Wiley
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI), Muscular Dystrophy Ireland, European Commission, Health Research Board (HRB)
URI:	http://onlinelibrary.wiley.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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