Fig. 3

Correction by leriglitazone of both bioenergetics and oxidative stress in Rett fibroblasts. A Schematic representation of leriglizatone (LGZ) and its activity as a PPARγ agonist in a cell. LGZ binds to PPARγ, activating the expression of the genes under its regulation through interaction with PGC1α. B LGZ effect was evaluated first on Rett fibroblasts at two concentrations, 100 nM and 500 nM for 48 h. C PPARγ pathway activation has an effect on the detection of all electron-transport chain complexes, detected by Western blot and densitometry quantification corrected by vinculin. The ultimate goal of LGZ treatment was to correct the previously described alterations, observing significant corrections in ATP (D), ROS production (E) and (F) oxidative damage measured in terms of 8-OHdG detection. Images are shown with the intensity-revealing LUT “royal”, at a 63× magnification; scale bar represents 10 µm. Images were quantified and statistical significance of corrections was evaluated (G). All experiments were done in at least two different control and Rett cell lines, with three technical replicates and each experiment was done in triplicates. Statistical analysis was performed as described in Materials and Methods. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Absence of asterisk means no statistically significant difference. Control fibroblasts in grey; Rett patients’ fibroblasts in yellow; LGZ-treated Rett patients’ fibroblasts in green