T0901317 as an Inhibitor of Transcriptional Activation of Constitutive Androstane Receptor (CAR)

국문 초록 (Abstract)

T0901317은 핵수용체 전사인자인 liver X receptor (LXR, NR1H2/3)의 강력한 합성 리간드이다. 그러나, T0901317은 farnesoid X receptor (FXR, NR1H4)와 pregnane X receptor (PXR, NR1I2)에 대해 작용물질(agonist)로, androgen receptor (AR, NR3C4)와 rertinoid-related orphan receptor-α (ROR-α, NR1F1)에 대해 길항제(antagonist)로 작용하여, LXR외에 적어도 다른 4종의 핵수용체에 대해 그 활성을 조절한다고 보고되었다. 우리는 T0901317이 또 다른 핵수용체인 constitutive androstane receptor (CAR, NR1I3)에 대해 저해제로 기능함을 확인하였다. CAR는 이미 T0901317에 의해 기능이 조절된다고 알려진 PXR, FXR, LXR과 더불어 간에서 생체이물과 콜레스테롤의 대사작용에 중요한 역할을 하므로 T0901317에 의해 CAR의 활성이 조절된다는 사실은, 간세포에서 T0901317을 이용한 실험결과를 해석할 때 세포 내에 이미 존재하는 이들 핵수용체 단백질의 영향을 고려하여 주의깊게 해석해야 함을 의미한다.

다국어 초록 (Multilingual Abstract)

T0901317 is a potent synthetic ligand for liver X receptor (LXR, NR1H2/3), a member of the nuclear receptor superfamily that functions as a transcription factor. However, T0901317 has been also reported to modulate the activity at least four other nuclear receptors (NRs), acting as agonists for farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2) and as antagonists for androgen receptor (AR, NR3C4) and retinoid-related orphan receptor-α (ROR-α, NR1F1). We report here that T0901317 can also function as an inhibitor for constitutive androstane receptor (CAR, NR1I3). Since CAR is a major player of xenobiotic and cholesterol metabolism in the liver, along with PXR, FXR and LXR, which are reported to be regulated by T0901317, this further complicates the interpretation of potential results with T0901317 in liver cells.

목차 (Table of Contents)

• Introduction
• Materials and Methods
• Results
• Discussion
• Acknowledgements
• References
• 초록

참고문헌 (Reference)

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