DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2009-07-27 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Tassin Alexandra , Coppée Frédérique , Leroy Baptiste , Erculisse V., Sauvage Sébastien, Charron Sébastien , Vanderplanck Céline, Barro Marietta, Vander Elst Luce , Muller Robert , Laoudj-Chenivesse Dalila, Colet Jean-Marie , Wattiez Ruddy , Belayew Alexandra , "Investigations on the molecular mechanism of a muscular dystrophy (FSHD) by proteomic and metabonomic analyses of primary myoblast cultures" in International Symposium Signal transduction and disease, Aachen, Allemagne, 2009

  • Codes CREF : Sciences biomédicales (DI3200), Biologie moléculaire (DI3111), Pathologies particulières (DI3370), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Biologie moléculaire (M122), Biologie humaine et Toxicologie (M125), Protéomie et Microbiologie (S828)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Facioscapulohumeral muscular dystrophy (FSHD) is a dominant genetic disease linked to deletions in an array of 3.3-kb repeated elements named D4Z4 on chromosome region 4q35. Non affected individuals present 11-150 D4Z4 copies while patients only have 1-10 copies. We identified a double homeobox gene (DUX4) within each D4Z4 unit that is activated in muscle cells following the FSHD deletion. The DUX4 protein is a transcription factor that targets a number of genes, some of which encode other transcription factors. Among others, DUX4 inhibits MYOD, leading to myoblast differentiation defects, activates PITX1 that induces muscle atrophy, and inhibits genes involved in response to oxidative stress. Several studies investigated gene /protein expression in FSHD primary myoblasts or muscle biopsies. Since DUX4 is activated upon myoblast differentiation, we chose to compare the proteome of FSHD and control myotubes by gel free differential mass spectrometry analysis using an isotope coded protein labelling (ICPL). In keeping with an FSHD differentiation defect we observed increased amounts of vimentin and galectin-1 that were confirmed by specific immunodetection on Western blots. We found a general decrease of cytoskeletal and contractile proteins that could reflect an atrophy-associated proteolysis as well as differentiation defects. Our data also confirmed a mitochondrial dysfunction in FSHD: enzymes involved in fatty acid ß-oxidation, Kreb’s cycle and the electron transport chain were decreased. There was no change in glycolytic enzymes but an increase of lactate dehydrogenase that correlated with lactate accumulation in the culture medium as observed by a metabonomics analysis (proton Nuclear Magnetic Resonance spectra).