Table 3.
Effect of CDCA Treatment on Protein Levels of Bile Acid Transporters and Metabolizing Enzymes in Sandwich-cultured Human Hepatocytes (SCHH)
| Transporter | Log10 Ratio | Fold Change | Metabolizing Enzyme | Log10 Ratio | Fold Change |
|---|---|---|---|---|---|
| Upregulated proteins | |||||
| OSTα | 1.7 | 51 | SULT1A1 | 0.29 | 1.9 |
| OSTβ | 0.91 | 8.2 | UGT1A1 | 0.19 | 1.5 |
| BSEP | 0.82 | 6.6 | UGT2A3 | 0.13 | 1.3 |
| MRP3 | 0.20 | 1.6 | UGT2B4 | 0.13 | 1.3 |
| MRP4 | 0.040 | 1.1 | UGT2B15 | 0.11 | 1.3 |
| MRP2 | 0.0037 | 1.0 | UGT1A3 | 0.064 | 1.2 |
| UGT1A4 | 0.038 | 1.1 | |||
| SULT2A1 | 0.026 | 1.1 | |||
| UGT2B7 | 0.023 | 1.1 | |||
| UGT1A6 | 0.021 | 1.0 | |||
| Downregulated proteins | |||||
| NTCP | −0.32 | 0.48 | CYP3A4 | −0.30 | 0.51 |
| OATP1B3 | −0.17 | 0.68 | UGT1A9 | −0.16 | 0.70 |
| OATP1B1 | −0.10 | 0.79 | SULT1A3 | −0.065 | 0.86 |
| UGT2B17 | −0.039 | 0.91 | |||
Quantitative targeted absolute proteomics analysis was performed on membrane protein (from duplicate or triplicate cell culture wells) extracted from two SCHH donors (WWQ and HU8246). The average fold change (relative to DMSO treatment) in protein levels across both donors was calculated using the protein concentrations shown in Figure 4C and Supplementary Figure 2.
Abbreviations: BSEP, bile salt export pump; CDCA, chenodeoxycholate; CYP, cytochrome P450; DMSO, dimethyl sulfoxide; MRP, multidrug resistance-associated protein; NTCP, sodium taurocholate cotransporting polypeptide; OATP, organic anion transporting polypeptide; OST, organic solute transporter; SULT, sulfotransferase; UGT, uridine 5′-diphospho-glucuronosyltransferase.