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Updated: May 29, 2026
10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Energy sensing factors PGC-1α and SIRT1 modulate PXR expression and function
Marcin Buler1, Sanna-Mari Aatsinki, Réka Skoumal
1Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, 90014 Oulu, Finland.
Biochemical Pharmacology
|September 22, 2011
Summary
Fasting-activated pathways, peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) and sirtuin 1 (SIRT1), differentially regulate pregnane X receptor (PXR) expression and function, impacting drug metabolism and hepatic energy homeostasis.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- The pregnane X receptor (PXR) is a key regulator of drug metabolism and hepatic energy homeostasis.
- Little is known about how cellular energy sensors influence PXR activity.
- PGC-1α and SIRT1 are critical regulators of hepatic energy metabolism.
Purpose of the Study:
- To investigate the effects of PGC-1α and SIRT1 on PXR expression and function.
- To elucidate the role of these energy regulators in PXR-mediated metabolic pathways.
Main Methods:
- Primary mouse hepatocytes were used to study PXR expression.
- Gene knockdown (siRNA) and overexpression techniques were employed.
- Mammalian two-hybrid and immunoprecipitation assays assessed protein interactions.
Main Results:
- Fasting, glucagon, and PGC-1α upregulate PXR expression.
- PGC-1α potentiates PXR-mediated induction of CYP3A11.
- Pyruvate, activating SIRT1, inhibits PGC-1α/PXR synergistic activity by interfering with PXR-PGC-1α interaction.
- SIRT1 was shown to interact directly with PXR.
Conclusions:
- PGC-1α and SIRT1, activated during fasting, differentially modulate PXR expression and function.
- These interactions highlight a novel regulatory mechanism linking hepatic energy status to PXR activity and drug metabolism.
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