Identification of the novel splicing variants for the hPXR in human livers

The human pregnane X receptor (hPXR) plays a key role in the regulation of both drug metabolism and efflux by inducing the expression of CYP3A4 and MDR1 gene. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we identified seven novel splicing variants of hPXR in tissue from a...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-11, Vol.298 (3), p.433-438
Main Authors: Fukuen, Shuichi, Fukuda, Tsuyoshi, Matsuda, Hideyasu, Sumida, Akihiko, Yamamoto, Isamu, Inaba, Tadanobu, Azuma, Junichi
Format: Article
Language:English
Subjects:
Alternative Splicing
Base Sequence
CYP3A4
DNA Primers
Drug metabolism
hPXR
Human liver
Humans
Liver - metabolism
P-Glycoprotein
Pregnane X Receptor
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Steroid - genetics
Reverse Transcriptase Polymerase Chain Reaction
RT-PCR
Splicing variant
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Summary:The human pregnane X receptor (hPXR) plays a key role in the regulation of both drug metabolism and efflux by inducing the expression of CYP3A4 and MDR1 gene. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we identified seven novel splicing variants of hPXR in tissue from a single human liver. The expression of hPXR-related transcripts in the liver samples of 15 Caucasian individuals was subsequently determined by RT-PCR assays. The pattern of expression levels of these transcripts varied among liver samples. These results suggest that the hPXR is expressed as several different transcripts in liver tissues, apparently due to alternative as well as defective gene splicing. Furthermore, because this study provides the possibility of interindividual differences in hPXR transcript profiles, these alternative splicings for hPXR may largely contribute to the interindividual variability in CYP3A4 and P-glycoprotein induction.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)02469-5