TABLE 3

Absolute protein levels and enzyme activities in sandwich cultures from donor preparation HuHep10536 after 48 h of treatment with solvent control and prototypical inducers OME, PB, and RIF, respectively

Protein concentrations (except for Na/K-ATPase) were normalized to γ-GTP for each incubation condition. P450 enzyme activities were determined in situ by measuring phenacetin O-deethylation (CYP1A2), bupropion 2-hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), and testosterone-6β hydroxylation (CYP3A4).

TargetControl50 μM OME1 mM PB25 μM RIF
Protein (±S.D.)Activity (±S.D.)Protein (±S.D.)Activity (±S.D.)Protein (±S.D.)Activity (±S.D.)Protein (±S.D.)Activity (±S.D.)
fmolgpmol · min1 · mio cells1fmolgpmol · min1 · mio cells1fmolgpmol · min1 · mio cells1fmolgpmol · min1 · mio cells1
CYP1A26.2 ± 1.1627.9 ± 0.59118.5 ± 16.0333.5 ± 19.916.1 ± 3.0768.5 ± 2.94.6 ± 0.4123.8 ± 1.8
CYP2B60.3 ± 0.054.0 ± 0.260.7 ± 0.1610.8 ± 0.72.3 ± 0.5935.8 ± 3.00.5 ± 0.0712.3 ± 0.4
CYP2C88.4 ± 1.37265.0 ± 9.468.9 ± 1.60182.3 ± 8.325.9 ± 23.6367.4 ± 13.88.6 ± 0.82289.3 ± 10.8
CYP2C945.7 ± 2.7162.0 ± 4.2375.5 ± 9.8541.9 ± 3.92
CYP2C194.1 ± 0.392.3 ± 0.423.4 ± 0.844.4 ± 0.46
CYP2D64.6 ± 0.462.7 ± 0.892.5 ± 0.822.5 ± 0.45
CYP3A4*9.2 ± 2.00210.0 ± 8.0258.7 ± 6.84650.6 ± 14.8139.5 ± 18.91358.0 ± 42.482.2 ± 6.321318.5 ± 98.8
CYP3A430.1 ± 0.040.1 ± 0.040.0 ± 0.040.1 ± 0.01
UGT1A112.7 ± 0.8436.2 ± 1.6533.4 ± 1.5316.8 ± 1.21
UGT2B735.8 ± 1.1850.0 ± 5.9844.9 ± 3.5521.5 ± 1.29
Na/K-ATPase7.8 ± 1.0010.1 ± 1.339.7 ± 2.854.4 ± 0.30
γ-GTP3.5 ± 0.724.5 ± 1.225.3 ± 1.002.8 ± 0.41
MDR11.3 ± 0.104.2 ± 0.385.6 ± 0.741.9 ± 0.04
BCRP0.3 ± 0.080.6 ± 0.110.6 ± 0.050.2 ± 0.01
MRP24.3 ± 0.437.6 ± 0.5610.4 ± 0.083.2 ± 0.23
NTCP2.7 ± 0.953.1 ± 1.342.4 ± 0.921.5 ± 0.24
OCT111.9 ± 0.8715.0 ± 0.3619.7 ± 1.086.9 ± 0.13
OATP1B30.8 ± 0.241.0 ± 0.301.2 ± 0.540.7 ± 0.15
OATP2B11.1 ± 1.001.6 ± 1.901.4 ± 1.430.9 ± 0.94
OATP1B10.7 ± 0.141.2 ± 0.371.0 ± 0.210.9 ± 0.12
  • * CYP3A4 protein was determined indirectly by CYP3A4 = CYP3A4/CYP3A43 − CYP3A43.