Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoprotective Autophagy

Figure 6

Geranylgeraniol (GGOH) does not rescue C2C12 myoblasts from GGTI-286-induced (IC₅₀) compromised cell viability. GGTI-286 was used as a specific inhibitor of protein geranylgeranyltransferases. C2C12 myoblasts were exposed for 24, 72, or 120 h to GGTI-286 (day 1—proliferating myoblasts, day 3—differentiating myotubes, and day 5—differentiated myotubes). GGTI-286 (IC₅₀): day 1—25 μM, day 3—24 μM, and day 5—23 μM or vehicle control (0.1% DMSO or 2% HS DMEM) without or with GGOH. GGOH (10 μM) could not reverse the drop in cell viability induced by GGTI-286. Two-way ANOVA test [time (proliferating myoblasts, differentiating myotubes, differentiated myotubes)] amounted to , ; treatment: GGTI-286, GGOH, and GGTI-286 + GGOH: , ; interaction: , , followed by Bonferroni’s multiple comparisons employed to analyze the data. Error bars = SEM and , , and for comparison between the means. Results are means of three independent experiments.