Silencing of SMRT cannot rescue the impaired function of
hPXRT57D. A, hPXRT57D colocalizes with SMRT to the
nucleus at discrete nuclear foci. COS7 cells were transfected with
FLAG-hPXRT57D. Twenty-four hours post-transfection, the cells were
treated with vehicle 0.1% DMSO or 10 μM rifampicin. The cells were
processed for immunocytochemistry 24 h after treatment with DMSO or
rifampicin. FLAG-hPXRT57D was probed using rabbit anti-hPXR
polyclonal antibody; SMRT was probed using anti-SMRT mouse monoclonal
antibody; and nuclear DNA was stained with Hoechst dye. Data shown are from a
representative experiment. B, Accell SMARTpool human SMRT siRNA knocks down
the protein expression of SMRT. HepG2 and COS7 cells were transfected with 1
μM Accell nontargeting pool control siRNA (lane 2) or Accell SMARTpool
human SMRT siRNA (lane 3) in Accell siRNA delivery media. Whole cell lysates
were collected 72 h after transfection and subjected to Western blotting
analysis using anti-SMRT and anti-actin antibodies. Protein expression for
SMRT without transfection was shown in lane 1. Actin protein expression was
shown as a loading control. Data shown are from a representative experiment.
C, silencing of SMRT cannot rescue the impaired transactivation function of
hPXRT57D. HepG2 and COS7 cells were transfected with
pcDNA3-FLAG-PXRT57D, pGL4-hRluc, and pGL3-CYP3A4-luc using
Lipofectamine. Five hours after transfection with the plasmids, the cells were
transfected with 1 μM Accell nontargeting SMARTpool control siRNA or Accell
SMARTpool SMRT siRNA in Accell siRNA delivery media for 72 h. Forty-eight
hours after transfection with the siRNAs, the cells were treated with vehicle
DMSO (0.1%) or 10 μM rifampicin. Firefly and Renilla luciferase
activities were measured 24 h after rifampicin treatment. Firefly luciferase
activity was first normalized with Renilla luciferase activity before
normalizing the data for rifampicin with DMSO. Data are shown as mean values
from four independent experiments with bars indicating the S.D. The Student's
t test was used to determine statistical significance of unpaired
samples by comparing the RLU obtained from the samples transfected with
control siRNA or SMRT siRNA with the samples that were not transfected with
siRNA. Differences were considered nonsignificant (N.S.) for p >
0.05.