Fig. 4: Stabilization of p53 is sufficient to induce myofiber dysfunction in in vitro differentiated and ex vivo Lmna WT myofibers. | Cell Death Discovery

Fig. 4: Stabilization of p53 is sufficient to induce myofiber dysfunction in in vitro differentiated and ex vivo Lmna WT myofibers.

From: Eliminating elevated p53 signaling fails to rescue skeletal muscle defects or extend survival in lamin A/C-deficient mice

Fig. 4

A Representative image of p53 nuclear immunofluorescence following 24 h of treatment with increasing concentrations of nutlin-3 (MDM2 inhibitor). Note the decrease in cell viability with increasing concentrations of nutlin-3. Scale bar: 25 µm. B Schematic of experimental design for nutlin-3 treatment in in vitro differentiated Lmna WT myofibers. C Quantification of myofiber viability using the MTT assay. Cells were treated with 2.5 µM nutlin-3 and/or 50 µM Z-DEVD-FMK (caspase-3 inhibitor) starting at day 5 of differentiation. (N = 5–6 independent replicates from n = 3 independent cell lines; data shown as mean ± SEM; One-way ANOVA with Tukey’s post hoc correction. D Quantification of myofiber contractility in Lmna WT myofibers following 5 days of 2.5 µM nutlin-3. (N = fields of view in n = 3 independent cell lines; data shown as mean ± SEM; unpaired Student’s t test). E Schematic of experimental design for nutlin-3 treatment in ex vivo Lmna WT muscle fibers. F Quantification of the percent sarcomere shortening in response to electrical stimulation in myofibers treated with different concentrations of nutlin-3 or DMSO control. (Data based on N = 3 mice and n = 38–55 muscle fibers; data shown as mean ± SEM; one-way ANOVA with Dunnett’s post hoc correction).

Back to article page