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RAGE-NF-kappaB pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy.

AbstractOBJECTIVES: An increased expression of adenine nucleotide translocator (ANT1), found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a decrease in nuclear factor-kappaB (NF-kappaB) DNA binding and to sensitize muscle cells to oxidative stress and apoptosis. Receptor for advanced glycation end products (RAGE) mediated by NF-kappaB activation is involved in proinflammatory pathomechanism and in muscle fiber regeneration in inflammatory myopathies and in limb girdle muscular dystrophy. Oxidative stress can stimulate RAGE- NF-kappaB pathway. Our purpose was to verify if oxidative stress may induce RAGE- NF-kappaB pathway activation in FSHD, contributing to the pathogenesis of such a disease. MATERIALS AND METHODS: On muscle samples of eight patients with FSHD, eight patients with Duchenne muscular dystrophy and eight normal controls the following studies were carried out: immunocytochemistry for activated NF-kappaB; electrophoretic mobility shift assay of NF-kappaB DNA binding activity; Western blot studies of RAGE and ANT1; hydrogen peroxide (HP), peroxidase and glutathione peroxidase (GPx) assays. RESULTS: An increased RAGE and ANT1 expression in FSHD with moderate increase of NF-kappaB DNA binding activity was found together with an increased production of HP and a reduced activity of peroxidase and GPx. CONCLUSIONS: Our data confirm that response to oxidative stress and ANT1 increased activity are early events in FSHD muscle. The study also reveals that the RAGE- NF-kappaB pathway, induced by oxidative stress, is activated independently of the presence of a clear histochemical evidence of muscle damage in FSHD.
AuthorsV Macaione, M Aguennouz, C Rodolico, A Mazzeo, A Patti, E Cannistraci, L Colantone, R M Di Giorgio, G De Luca, G Vita (Affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy. vmacaione at unime.it)
JournalActa neurologica Scandinavica (Acta Neurol Scand) Vol. 115 Issue 2 Pg. 115-21 (Feb 2007) ISSN: 0001-6314 Denmark
PMID17212615 (Publication Type: Journal Article)
Chemical References
  • Adenine Nucleotide Translocator 1
  • NF-kappa B
  • Receptors, Immunologic
  • advanced glycosylation end-product receptor
Topics
  • Adenine Nucleotide Translocator 1 (metabolism)
  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Electrophoretic Mobility Shift Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal (metabolism, pathology)
  • Muscular Dystrophy, Facioscapulohumeral (metabolism, pathology)
  • NF-kappa B (metabolism)
  • Oxidative Stress (physiology)
  • Receptors, Immunologic (metabolism)