RAGE‐NF‐ κ B pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy

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.