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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy is the most commonly inherited neuromuscular disorder in humans. Although the primary genetic deficiency of dystrophin in X-linked muscular dystrophy is established, it is not well-known how pathophysiological 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, beta-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 and may be exploitable as a new approach to counteract muscle degeneration.
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PMID:Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP. 1683 51

In contrast to the traditional biochemical study of single proteins or isolated pathways in health and disease, technical advances in the high-throughput screening of peptides by mass spectrometry have established new ways of identifying entire cellular protein populations in one swift analytical approach. This review discusses the recent progress in the biochemical analysis of skeletal muscle extracts and outlines the mass spectrometry-based proteomics approach for studying muscle tissues in normal and pathobiochemical processes using peptide mass fingerprinting. Individual topics covered include the most commonly inherited muscle disease, X-linked muscular dystrophy, the physiological process of fast-to-slow fibre transformation, and the role of fibre degeneration in age-related muscle wasting. Recent proteomic profiling studies of dystrophic muscles have revealed new disease markers in dystrophin-deficient fibres, such as adenylate kinase, the Ca2+-binding protein regucalcin and the small heat shock protein cvHSP. Since these muscle proteins are of low abundance, they have not previously been identified as biomarkers of muscular dystrophy, illustrating the increased sensitivity of modern mass spectrometric techniques. This review outlines comparative proteomic techniques that employ conventional labeling methods, such as Coomassie- or silver-staining. In addition, the most advanced proteomic screening approach currently available, fluorescence difference in-gel electrophoresis, is described and its potential for studying muscle proteomes is critically examined. As an alternative suggestion, the two-dimensional analysis of different protein samples separated in parallel on a single second dimension gel is introduced and the usefulness of this technique for direct comparative investigations is explained. The potential of studying protein complex formation by intraproteomics, estimating the composition of subcellular fraction by subproteomics, and analyzing total muscle protein extracts by mass spectrometry-based proteomics, is enormous. Proteomics is one of the most promising new analytical ways of comparing large muscle protein complements and has the potential to decisively improve modern biochemical and biomedical research into neuromuscular disorders.
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PMID:Proteomic profiling of pathological and aged skeletal muscle fibres by peptide mass fingerprinting (Review). 1733 30