Article Figures & Data
Figures
- Fig. 1.
Total hepatic transporter abundance in LT, SH, PH, and SCH. There was no significant difference in the total abundance of uptake transporters OATP1B1/2B1/1B3, OCT1, and OAT2 between LT, SH, PH, and SCH. In contrast, total abundance of the efflux transporters MRP2, MRP3, and P-gp was significantly greater in SCH vs. LT. NTCP and BSEP abundance was significantly higher in PH vs. LT. Data for each donor are mean ± S.D. of three to five independent experiments (only single experiment for NTCP). *P < 0.05; **P < 0.01.
- Fig. 2.
Percentage of plasma membrane abundance of hepatic transporters in SH, PH, and SCH. Hepatic uptake transporters (OATP1B1/2B1/1B3, NTCP, OCT1, OAT2) were mostly (>50%) localized in the plasma membrane of SH, PH, or SCH. P-gp and BSEP were mostly localized intracellularly in SH and PH, but in SCH, the localization in the plasma membrane of P-gp, but not BSEP, increased significantly to >50%. Na+-K+ ATPase and calreticulin were used as a positive control for plasma membrane and intracellular (endoplasmic reticulum) marker, respectively. Cell surface biotinylation experiment was conducted in presence of calcium-containing Hanks’ balanced salt solution buffer. Data are reported as mean ± S.D. of four hepatocyte donors (except SCH-NTCP: three donors), with data for each donor as the mean of three independent experiments (only single experiment for NTCP). *P < 0.05.
- Fig. 3.
Plasma membrane abundance of hepatic transporters in SH, PH, and SCH. Values are expressed as percentage of abundance relative to the respective SH (derived from Figs. 1 and 2). Of the transporters studied, the PMA of MRP2, MRP3, and P-gp was significantly higher in SCH vs. SH. Data for each donor are reported as mean of three to five independent experiments (only single experiment for NTCP). *P < 0.05.
- Fig. 4.
Correlation of total transporter abundance across LT, SH, PH, and SCH. The total abundance of MRP2, MRP3, and P-gp was highly correlated with each other [(A–C), R2 ≥ 0.88]. OAT2 and OCT1 abundance showed good correlation with OATP1B1 and OATP2B1 [(D and E), R2 ≥ 0.67], respectively, but the abundance of OAT2 was poorly correlated (R2 ≤ 0.5) with OATP1B3 [(F); representative of those showing poor correlation—see Supplemental Table 3]. Each datum is mean of three to five independent experiments.
Additional Files
Data Supplement
- Supplemental Data -
3 supplemental figures, 4 tables.
- Supplemental Data -
