Figure 2.

Effect of inhibitors on CoQ₁₀ transport across bEnd.3 BBB model. CoQ₁₀ (pre-incubated in serum) transport across bEnd.3 cells on Transwell filters assayed over 60 min. Inhibitors added apically and basally two hours before assay were BLT-1 (10 µM) for SR-B1, FPS-ZM1 (1 µM) for RAGE, receptor-associated protein (RAP) (0.5 µM) for LRP-1/LDLR and verapamil (0.1 mM) for p-glycoprotein. Apparent permeability, Papp, shown for (a) Apical to Basal CoQ₁₀ transport, (b) Basal to Apical CoQ₁₀ transport. (c) The “net” transport of CoQ₁₀ across bEnd.3 cells, calculated from the difference between A to B transport (blood-to-brain) and B to A transport (brain-to-blood). “Net” transport in control cells did not differ from zero (95% confidence interval). * Treatment with SR-B1 or RAGE inhibitors (BLT-1 10 µM, FPS-ZM1 1 µM) resulted in “net” −ve transport, i.e., “net” transport directed toward the blood side (B to A). ^† Treatment with LRP-1/LDLR inhibitor RAP (0.5 µM), resulted in “net” +ve transport toward the brain side (A to B). The p-glycoprotein efflux transport inhibitor Verapamil (0.1 mM) had no significant effect. (d) Schematic summary of CoQ₁₀ transport across the BBB. No “net” CoQ₁₀ entry toward brain side. Uptake by RAGE and SR-B1, is opposed by LRP-1/LDLR mediated removal to blood, a major impediment to brain entry of CoQ₁₀. (e) Transport of the CoQ₁₀ analogue, Idebenone (10 µM). Apical to basal transport exceeded basal to apical, meaning there was “net” transport toward the brain. n = 4-5, Values are mean ± SEM * p < 0.05. (f) FITC-40 Apical to Basal transport; n = 8 (control), n = 4–5 (interventions); values are mean ± SEM; * p < 0.05, ** p < 0.01; ANOVA single factor; post-hoc Bonferroni.