Skip to main content
. Author manuscript; available in PMC: 2022 Jan 1.
Published in final edited form as: Biochem Pharmacol. 2020 Nov 25;183:114349. doi: 10.1016/j.bcp.2020.114349

Figure 7-. Geranylgeranylation inhibition enhances 5-HT uptake independent of simvastatin, is SERT-dependent.

Figure 7-

A.) Geranylgeranyl transferase Type 1 (GGTase) inhibitor GGTI-298 dose-dependently increases 5-HT uptake at concentrations up to IC70 inhibitor concentrations (10μM GGTI-298). Results were quantified as pg 5-HT/μg protein and normalized to % Veh. (n=4/grp, 1-Way ANOVA significant GGTI-298 effect (p<0.001), *p<0.01 Tukey’s Post-Hoc comparison to Veh. B.) Farnesyl Transferase (FTase) inhibitor I up to the IC70 inhibitor concentration (500nM Farnesyl Transferase Inhibitor I) does not enhance 5-HT uptake (n=3/grp, One-Way ANOVA not significant). C) SERTMyc cells post-fixed after 5-HT uptake assay and stained for 5-HT. Prior to 5-HT uptake assay and fixation, SERTMyc cells were treated with Vehicle, 1, 2, 4, and 10μM GGTI-298 for 24hr. D) 10μM GGTI increases 5-HT uptake more than 0.5μM simvastatin, without changing basal 5-HT (n=4/grp, 2-Way ANOVA with Tukey’s Post-Hoc comparison to Veh *p<0.05, or comparing Sim and GGTI #p<0.001). E.) Enhanced 5-HT uptake by 10μM GGTI-298 applied for 24hr was blocked by 1μM of the SERT inhibitor fluoxetine, applied 30min prior to 5-HT uptake (n=3/grp, 2-Way ANOVA significant Fluoxetine effect (p<0.01), #p<0.05 Tukey Post-Hoc comparison to Veh,Veh, *p<0.001 Tukey Post-Hoc comparison to 10μM GGTI-298). F.) SERTMyc cells post-fixed after 5-HT uptake assay and stained for 5-HT. Prior to 5-HT uptake assay and fixation, SERTMyc cells were treated with or without 10μM GGTI-298 for 24hr followed by 1μM fluoxetine applied 30min prior to 5-HT uptake Data are represented as mean ± SEM. Veh= Vehicle, Fluox= Fluoxetine, GGTI=Geranylgeranyl transferase type 1 inhibitor GGTI-298, GGTase=Geranylgeranyl Transferase 1, FTase=Farnesyl Transferase.