title: RAGE-NF-kappaB pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy. vmacaione@unime.it
authors.forename: V
authors.initials: V
authors.lastname: Macaione
authors.forename: M
authors.initials: M
authors.lastname: Aguennouz
authors.forename: C
authors.initials: C
authors.lastname: Rodolico
authors.forename: A
authors.initials: A
authors.lastname: Mazzeo
authors.forename: A
authors.initials: A
authors.lastname: Patti
authors.forename: E
authors.initials: E
authors.lastname: Cannistraci
authors.forename: L
authors.initials: L
authors.lastname: Colantone
authors.forename: R M
authors.initials: RM
authors.lastname: Di Giorgio
authors.forename: G
authors.initials: G
authors.lastname: De Luca
authors.forename: G
authors.initials: G
authors.lastname: Vita
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D033741:Adenine Nucleotide Translocator 1; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic