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, Figure 3. GSK773 corrects the impaired differentiation process in CPT2-deficient myotubes

, Representative kinetics of muscle cells during proliferation and differentiation using xCELLigence system

, Histograms of cell index at different times; (n=6-10 experiments)

, Representative kinetics of muscle cells treated with 30µM GSK773 during proliferation and differentiation, the blue arrows represent the treatments

, Maximum cell index of myotubes treated for 10 days

, Representative immunofluorescence images: MHC-I (green), CPT2 (red) and Topro-3-labeled nuclei (blue)

, Fatty acid oxidation flux measured in myotubes treated for 10 days

, Data are means ± SEM. *p<0.05, **p<0.01 compared with vehicle-treated myotubes

, AMPK is constitutively phosphorylated in CPT2 patients, and AMPK and PGC-1? are involved in signaling pathway triggered by GSK773

, Representative western blots of AMPK?1 and P-AMPK (n=4-6 experiments)

, Quantification of P-AMPK protein levels in myotubes (30 µM GSK773, 48h)

P. Ratio,

, Representative western blots of AMPK?1, CPT2 and MHC-I. Myotubes were transfected with siNon-target (NT) or siAMPK?1 at day 2 of differentiation, were allowed to differentiate 2 more days and were then treated with 30 µM GSK773 for 48h

, Quantification of CPT2 protein levels in transfected myotubes

, Quantification of MHC-I protein levels in transfected myotubes

, Representative western blots of CPT2 and MHC-I from myotubes transfected with siNon-target (NT) or siPGC-1?, and treated with 30 µM GSK773 for 48h

, Quantification of CPT2 protein levels in transfected myotubes (n= 5 independent experiments)

, Quantification of MHC-I protein levels in transfected myotubes (n= 3-5 independent experiments)

, Data are means ± SEM. *p<0.05, **p<0.01, ***p<0.001 versus vehicle-treated myotubes, p.33

, Figure 5. ROS and p38-MAPK are involved in signaling pathway triggered by GSK773

, Relative measurement of total cellular reactive oxygen species (ROS) production in myotubes, after 48h of treatment with 30µM GSK773 (n=3 independent experiments)

, Representative fluorescence images of myotubes loaded with the ROS sensor CM-H2DCFDA

, Representative western blots of p38-MAPK and P-p38-MAPK (n=3 different experiments)

, Quantification of P-p38 protein levels in myotubes (30 µM GSK773, 48h)

, Representative western blots of CPT2 and MHC-I from myotubes treated with 30µM GSK773 for 48h in conjunction with 10mM N-acetyl-cysteine (NAC) or 10µM SB203580 (myotubes were pre-treated with the p38 inhibitor 30min prior addition of GSK773)

, Quantification of CPT2 protein levels (n= 4 independent experiments

, Quantification of MHC-I protein levels (n=4 independent experiments)

, Proposed schematic model of the effects of GSK773 on CPT2 and MHC-I

, Data are means ± SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 compared with vehicle-treated myotubes

, Figure 6. GSK773 acts on mitochondrial biogenesis and on mitochondrial network

, Quantification of citrate synthase protein levels in myotubes

, Quantification of Tfam and COX2 protein levels; (n=3-6 experiments)

, Immunofluorescence images of 10 days-treated myotubes: CPT2 (red) and Topro-3-labeled nuclei (blue) at x40 magnification and (D) x80 magnification

, Quantification of DRP1 protein levels in myotubes (30 µM GSK773, 48h); (n=4-6 experiments)

, Quantification of MFN2 protein levels in myotubes (30 µM GSK773, 48h); (n=5-6 experiments)

, Representative western blots of LC3-I and LC3-II (n=3 different experiments)

, Quantification of LC3-I + LC3-II protein levels

, Quantification of LC3-II protein levels