Cytochrome P-450 3A4 proximal promoter activity by histone deacetylase inhibitor in HepG2 cell.

  • Kim, Ja-Young (Ewha Womans University, College of Pharmacy, National Institute of Toxicological Research, Korea Food & Drug Administration) ;
  • Ahn, Mee-Ryung (Ewha Womans University, College of Pharmacy, National Institute of Toxicological Research, Korea Food & Drug Administration) ;
  • Sheen, Yhun-Yhong (Ewha Womans University, College of Pharmacy, National Institute of Toxicological Research, Korea Food & Drug Administration)
  • Published : 2003.10.01

Abstract

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. (omitted)

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