The pregnane X receptor down-regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for ("squelching") SRC-1 coactivator.

ABSTRACT:

Background and purpose

The organic cation transporter 1 (OCT1) transports cationic drugs into hepatocytes. The high hepatic expression of OCT1 is controlled by the HNF4α and USF transcription factors. Pregnane X receptor (PXR) mediates induction of the principal xenobiotic metabolizing enzymes and transporters in the liver. Here, we have assessed the down-regulation of OCT1 expression by PXR activation.

Experimental approach

We used primary human hepatocytes and related cell lines to measure OCT1 expression and activity, by assaying MPP(+) accumulation. Western blotting, qRT-PCR, the OCT1 promoter gene reporter constructs and chromatin immunoprecipitation assays were also used.

Key results

OCT1 mRNA in human hepatocytes was down-regulated along with reduced [(3) H]MPP

SUBMITTER: Hyrsova L 

PROVIDER: S-EPMC4842917 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature