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RAGE‐NF‐ κ B pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy
Author(s) -
Macaione V.,
Aguennouz M.,
Rodolico C.,
Mazzeo A.,
Patti A.,
Cannistraci E.,
Colantone L.,
Di Giorgio R. M.,
De Luca G.,
Vita G.
Publication year - 2007
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.2006.00724.x
Subject(s) - facioscapulohumeral muscular dystrophy , oxidative stress , endocrinology , medicine , rage (emotion) , proinflammatory cytokine , glutathione peroxidase , muscular dystrophy , duchenne muscular dystrophy , biology , superoxide dismutase , inflammation , neuroscience
Objectives – An increased expression of adenine nucleotide translocator (ANT1), found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a decrease in nuclear factor‐ κ B (NF‐ κ B) DNA binding and to sensitize muscle cells to oxidative stress and apoptosis. Receptor for advanced glycation end products (RAGE) mediated by NF‐ κ B 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‐ κ B pathway. Our purpose was to verify if oxidative stress may induce RAGE‐ NF‐ κ B 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‐ κ B; electrophoretic mobility shift assay of NF‐ κ B 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‐ κ B 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‐ κ B pathway, induced by oxidative stress, is activated independently of the presence of a clear histochemical evidence of muscle damage in FSHD.