Résumé :
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Oculo-pharyngeal muscular dystrophy (OPMD) is an adult onset disorder (40-50 years) characterised by progressive eyelid drooping (ptosis) and swallowing difficulties (dysphagia). This autosomal dominant disease is caused by an amplification of a GCG repeat in the PABPN1 gene from 8 to 13 repeats which results in the expansion of a polyalanine stretch in the N-terminus of the PABPN1 protein. The molecular mechanisms which cause only a few muscle groups to be specifically affected in OPMD patients are not yet understood. Previously we have shown that satellite cells isolated from Cricopharyngeal muscle (CP) of OPMD patients have a lower myogenecity and reduded proliferative life span compare to the cells isolated from healthy donors or from the unaffected Vastus lateralis (VL) of OPMD patients. In the present study, in order to find out consequences of mutated PABPN1 expression we performed two types of proteomic comparisons. In the first we compared the proteomes of myoblasts isolated of spared muscles (VL) from OPMD patients versus the same muscles from healthy donors. In the second analysis myoblasts from affected (CP) muscles were compared to myoblasts of healthy donors. Cytoplasmic and nuclear protein extracts from the myoblasts were separated by 2D gel electrophoresis and differentially expressed proteins were identified by MALDI-ToF mass spectrometry. We found that the number of differentially expressed proteins is substantially higher in the second type of analysis (83 versus 51) thus indicating a more important perturbation of the proteomie in the affected muscles. These differentially expressed proteins are involved in detoxification, energy metabolism, protein folding and also implicated in histone acetylation/deacetylation process. Our results indicate that histone deacetylases could be a possible therapeutic target for OPMD treatment.
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