Myoblast Survival Enhancement and Transplantation Success Improvement by Heat-Shock Treatment in MDX Mice

Bouchentouf, Manaf; Benabdallah, Basma; Tremblay, Jacques P.

doi:10.1097/01.tp.0000121503.01535.f5

Cited by 46 publications

(49 citation statements)

References 28 publications

(7 reference statements)

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“…That this is a realistic biomedical option has recently been shown in cellbased therapy approaches. Heat shock treatment appears to enhance the survival of transplanted myoblasts [55]. Since up-regulation of heat shock proteins represents an autoprotective mechanism during biological stress, the pharmacological or cell therapeutic enhancement of this natural response may be useful for counteracting excessive muscle wasting in X-linked muscular dystrophy.…”

Section: Discussionmentioning

confidence: 99%

Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP

et al. 2006

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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, 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 and may be exploitable as a new approach to counteract muscle degeneration.

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Section: Discussionmentioning

confidence: 99%

Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP

et al. 2006

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“…Since no proper diagnostic criteria exist yet for the differential diagnosis of severe sarcopenia versus mild age-related muscle weakness (Carmeli et al, 2002;Greenlund and Nair, 2003), the establishment of novel biomarkers of muscle degeneration may be helpful in developing diagnostic procedures with reliable indicators of aging-induced fibre degeneration. More importantly, since heat shock treatment of myoblasts was shown to improve their survival rate following transplantation in the experimental treatment of muscular dystrophy (Bouchentouf et al, 2004), the stress response in aged fibres may be exploitable as a new approach to counteract excessive muscle damage in sarcopenia of old age. The findings of this study suggest that the cell therapeutic or pharmacological enhancement of the heat shock response might be helpful for preventing age-related muscle wasting.…”

Section: Discussionmentioning

confidence: 99%

Aging skeletal muscle shows a drastic increase in the small heat shock proteins αB-crystallin/HspB5 and cvHsp/HspB7

Doran

Gannon

O’Connell

et al. 2007

European Journal of Cell Biology

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Most heat shock proteins operate as molecular chaperones and play a central role in the maintenance of normal cellular function. In skeletal muscle, members of the a-crystallin domain-containing family of small heat shock proteins are believed to form a cohort of essential stress proteins. Since aB-crystallin (aBC/HspB5) and the cardiovascular heat shock protein (cvHsp/HspB7) are both implicated in the molecular response to fibre transformation and muscle wasting, it was of interest to investigate the fate of these stress proteins in young adult versus aged muscle. The agerelated loss of skeletal muscle mass and strength, now generally referred to as sarcopenia, is one of the most striking features of the senescent organism. In order to better understand the molecular pathogenesis of age-related muscle wasting, we have performed a two-dimensional gel electrophoretic analysis, immunoblotting and confocal microscopy study of aged rat gastrocnemius muscle. Fluorescent labelling of the electrophoretically separated soluble muscle proteome revealed an overall relatively comparable protein expression pattern of young adult versus aged fibres, but clearly an up-regulation of aBC and cvHsp. This was confirmed by immunofluorescence microscopy and immunoblot analysis, which showed a dramatic age-induced increase in these small heat shock proteins. Immunodecoration of other major stress proteins showed that they were not affected or less drastically changed in their expression in aged muscle. These findings indicate that the increase in muscle-specific small heat shock proteins constitutes an essential cellular response to fibre aging and might therefore be a novel therapeutic option to treat sarcopenia of old age.

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“…Interestingly, heat shock treatment enhances the survival rate of transplanted myoblasts [128], demonstrating the important role of the stress response in muscle regeneration [129].…”

Section: Proteomic Profiling Of Dystrophic MDX Musclesmentioning

confidence: 99%

Proteomic profiling of animal models mimicking skeletal muscle disorders

Doran

Gannon

O’Connell

et al. 2007

Proteomics Clinical Apps

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Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping.

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Myoblast Survival Enhancement and Transplantation Success Improvement by Heat-Shock Treatment in MDX Mice

Abstract: The heat-shock treatment is a practical approach for improving the success of myoblast transplantation; in fact, using this kind of treatment, there is no need to genetically modify the cells before their transplantation.

Cited by 46 publications

References 28 publications

Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP

Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP

Aging skeletal muscle shows a drastic increase in the small heat shock proteins αB-crystallin/HspB5 and cvHsp/HspB7

Proteomic profiling of animal models mimicking skeletal muscle disorders

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