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- W2028651444 abstract "In normal skeletal myotubes, tetanic electrical stimulation activates NFκB through intracellular calcium increase released by inositol 1,4,5 triphosphate receptor (IP3R) and by Ryanodine receptors (RyR). In this work, we studied the differences in calcium transients evoked by electrical stimuli and NFκB activation in wild type (C57) and in mdx (animal model of Duchenne muscular dystrophy, DMD) myotubes. Myoblasts were obtained from C57 or mdx neonatal mice (1-3 days). Myotubes were loaded with fluo-3AM and stimulated with 250 pulses of 0.5 ms duration at 20 Hz and the calcium signal was assessed by fluorescence microscopy. NFκB activation was determined by luciferase reporter assay, p65 immunofluorescence and p65-GFP translocation. Fast calcium signal (RyR dependent) was significantly reduced in electrically stimulated mdx compared to wild type C57 myotubes (0.62 vs 1.41 RLU, p<0.01). However, the amplitude and kinetics of (IP3 dependent) slow calcium signals were similar in mdx and C57 myotubes. Electrical stimulation increased the NFκB luciferase activity in normal but not in mdx myotubes. By immunofluorescence, p65-GFP translocation studies and reporter assays we determined that the basal activity of this transcription factor is up-regulated in mdx myotubes and this could be blocked by inhibitors of IP3-related pathways (100 µM suramine, 10 µM BAPTA-AM, 5 µM xestospongin B) but not by ryanodine (30 µM). We propose that NFκB up regulation in mdx myotubes is modulated by intracellular calcium release through IP3R. The differences in NFκB activation between normal and dystrophic muscle cells may help to understand the mechanisms of pro-inflamatory cytokines gene expression in Duchenne muscular dystrophy. FONDAP 15010006, AFM14562. CONICYT graduate student fellowship and doctoral support AT-24100066." @default.
- W2028651444 created "2016-06-24" @default.
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- W2028651444 date "2011-02-01" @default.
- W2028651444 modified "2023-10-18" @default.
- W2028651444 title "Ip3-Dependent Calcium Transients Differentially Modulate Nf-Kappa B Activity in Wild Type and Mdx Myotubes" @default.
- W2028651444 doi "https://doi.org/10.1016/j.bpj.2010.12.642" @default.
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