Résumé :
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Hereditary inclusion body myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult onset and slowly progressive distal and proximal muscle and a typical histology including rimmed vacuoles and filamentous inclusions. The disease is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase (GNE), the key enzyme in the biosynthetic pathway of sialic acid. Here we present a proteome comparison between biopsies from 3 healthy individuals and 3 HIBM patients, matched by age, gender and muscle type, carried out in parallel by iTRAQ analysis and by two-dimensional gel electrophoresis.The iTRAQ method resulted in the identification by mass spectrometry of 150 proteins, several of them differentially expressed in HIBM patients versus controls. The 2D analysis detected 35 proteins differentially expressed in HIBM. Results were validated by regular western blots of the same specimens with antibodies of representative proteins. To examine the sialylation profile of the relevant glycoproteins, Western blots were also performed from the very same 2D gels with lectins and specific antibodies against highly sialylated proteins. These studies contribute to a more comprehensive knowledge on the expression and posttranslational modifications of proteins in muscle tissue in general, and to new insights in the understanding of the pathogenesis of HIBM.
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