A) SERTMyc cells treated with 0.5μM simvastatin for 24hr
significantly decreases the Michaelis-Menten Km, but does not change SERT uptake
Vmax (n=5/grp, *p<0.0001 t-test comparing vehicle vs.
simvastatin Km and Vmax). B) SERTMyc cells treated with 0.5μM simvastatin
for 24hr shifts SERT Ki at 100nM 5-HT, with increasing concentrations of SERT
inhibitor fluoxetine (n=4/grp, *p<0.05 t-test comparing
vehicle vs. simvastatin Ki). C) Simvastatin does not change densitometry
measures of SERT in total, membrane separated, and intracellular fractions after
0.5μM, 24hr simvastatin treatment. Representative blots demonstrate
enrichment of membrane localized pan-cadherin in membrane and total fractions
that is not present in the intracellular fraction, and intracellular fractions
with lamin B1. D) Mean values and SEM for SERT uptake Km and Vmax (from graph A)
and IC50 and Ki (from graph B) in vehicle and simvastatin-treated cells. Data
are represented as mean ± SEM. T=Total SERT, M and Mem=Membrane SERT, I
and Intra=Intracellular SERT, V=Vehicle, S=Simvastatin.