TABLE 1

Effect of CAR overexpression and DMSO treatment on transcript levels of HepaRG cells

Transcript levels of HepaRG ± CAR cells cultured with or without DMSO as the percentage of the mean transcript levels of two human liver samples. Transcript levels were assessed in one to six independent experiments of at least three separate samples in each group. The number of experiments is indicated in parentheses after the gene name.

GeneDescriptionHepaRG (DMSO−)HepaRG-CAR (DMSO−)HepaRG (DMSO+)HepaRG-CAR (DMSO+)
Transcription factor
CAR (6) Constitutive androstane receptor5.3 (±2.7)108 (±25)***15 (±14)******208 (±26)***,******,###
PXR (6) Pregnane X receptor20 (±10)18 (±11)37 (±23)*,*****25 (±16)
AHR (4) Aryl hydrocarbon receptor161 (±37)133 (±23)287 (±112)*,***** 308 (±123)**,******
HNF4α (3) Hepatocyte nuclear factor 4 α176 (±70)140 (±76)172 (±62)209 (±80)
FXR (3) Farnesoid X receptor123 (±27)89 (±5.0)*88 (±10)**94 (±21)*
Phase 1 drug metabolism
CYP1A2 (5) Cytochrome P450 1A20.04 (±0.02)0.04 (±0.05)0.59 (±0.35)***, ******0.51 (±0.43)**,*****
CYP2A6 (2) Cytochrome P450 2A64.5 (±1.7)10 (±4.3)5.9 (±2.1)7.1 (±2.5)
CYP2B6 (5) Cytochrome P450 2B62.5 (±1.3)136 (±93)33 (±20)874 (±548)***,******,###
CYP2C8 (2) Cytochrome P450 2C812 (±0.9)22 (±1.2)***9.8 (±2.9)******28 (±2.7)***,****,###
CYP2C9 (3) Cytochrome P450 2C98.9 (±2.3)18 (±8.9)35 (±10)*** 80 (±19)***,###
CYP2C19 (1) Cytochrome P450 2C1921 (±1.6)46 (±6.2)**32 (±5.4)96 (±9.1)***,*****,###
CYP2D6 (2) Cytochrome P450 2D61.9 (±0.3)1.8 (±0.3)4.4 (±3.3)4.3 (±3.4)
CYP2E1 (3) Cytochrome P450 2E10.12 (±0.04)0.06 (±0.03)0.83 (±0.31) ***,******0.09 (±0.02)###
CYP3A4 (5) Cytochrome P450 3A43.7 (±4.4)16 (±24)58 (±46)160 (±101) ***,******,###
AOX1 (4) Aldehyde oxidase 163 (±13)58 (±8.0)111 (±15)***,******128 (±28) ***,******
POR (6) Cytochrome P450 reductase54 (±13)78 (±17)81 (±23)*180 (±38) ***,******,###
Phase 2 drug metabolism
UGT1A1 (3) Uridine diphosphate glucuronosyltransferase 1 family. polypeptide A137 (±14)135 (±76)259 (±135)1595 (±866) ***,******,###
Membrane transporter
NTCP (4) Na+-taurocholate cotransporting polypeptide6.6 (±3.0)5.5 (±3.4)12 (±5.4)****13 (±7.2)*,*****
OATP1B1 (3) Organic anion-transporting polypeptide 1B15.3 (±1.9)4.0 (±2.1)4.8 (±1.9)4.7 (±3.0)
OATP2B1 (2) Organic anion-transporting polypeptide 2B183 (±15)71 (±10)59 (±13)*65 (±14)
MRP2 (2) Multidrug resistance-associated protein 277 (±21)117 (±42)145 (±61)*216 (±34)***,*****,#
MRP3 (1) Multidrug resistance-associated protein 3335 (±54)328 (±58)323 (±56)268 (±33)
Blood protein
ALB (1) Albumin47 (±6.7)63 (±8.2)41 (±7.7)****31 (±2.9)*****
Nitrogen metabolism
ARG1 (1) Arginase 14.9 (±0.4)4.4 (±1.0)4.9 (±0.9)0.8 (±0.0) ***,******,###
ARG2 (1) Arginase 2385 (±79)172 (±26)*654 (±62)**,******495 (±90)*****
CPS1 (1) Carbamoyl-phosphate synthase 19.0 (±0.9)11 (±0.7)**2.7 (±0.4) ***,******0.7 (±0.1)***,******,#
Heme synthesis
ALAS1 (2) 5′-Aminolevulinate synthase 123 (±5.0)34 (±5.9)*30 (±4.2)73 (±7.8)***,******,###
  • * P < 0.05; **P < 0.01; ***P < 0.001 versus HepaRG (DMSO−); ****P < 0.05; *****P < 0.01; ******P < 0.001 versus HepaRG-CAR (DMSO−); #P < 0.05; ##P < 0.01; ###P < 0.001 versus HepaRG (DMSO+).