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Updated: Oct 21, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu
Anushna Sen1, Sayeepriyadarshini Anakk1
1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Abstract:
Nuclear receptors (NRs) are ligand-binding transcription factors that regulate gene networks and physiological responses. Often oxidative stress precedes the onset of liver diseases, and Nrf2 is a key regulator of antioxidant pathways. NRs crosstalk with Nrf2, since NR activation can influence the oxidative milieu by modulating reductive cellular processes. Diet and xenobiotics also regulate NR expression and activity, suggesting a feedback loop. Depending on the tissue context and cues, NRs either increase or decrease toxicity and oxidative damage. Many FDA-approved drugs target NRs, and one could potentially repurpose them to ameliorate reactive oxygen species (ROS). Here, we discuss how several NRs modulate oxidative stress subsequent to diet, organic pollutants, and drug-induced injury to the liver.
Insights
Nuclear receptors (NRs) regulate gene networks and physiological responses. Their interaction with Nrf2 influences oxidative stress, offering potential therapeutic targets for liver diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- Oxidative stress is a key factor in liver disease development.
- Nuclear receptors (NRs) are crucial transcription factors involved in various physiological processes.
- Nrf2 is a master regulator of cellular antioxidant defenses.
Purpose of the Study:
- To explore the intricate crosstalk between nuclear receptors and the Nrf2 antioxidant pathway.
- To discuss how NRs modulate oxidative stress in the context of diet, pollutants, and drug-induced liver injury.
- To investigate the potential repurposing of FDA-approved NR-targeting drugs for managing reactive oxygen species (ROS).
Main Methods:
- Literature review and synthesis of existing research on NRs, Nrf2, and oxidative stress.
- Analysis of how dietary components, environmental pollutants, and xenobiotics affect NR activity and oxidative balance.
- Discussion of the dual role of NRs in either exacerbating or mitigating liver toxicity.
Main Results:
- NRs significantly influence the cellular oxidative milieu through modulation of reductive processes.
- NR activity and expression are regulated by diet and xenobiotics, indicating a feedback loop.
- NRs exhibit context-dependent effects on liver toxicity and oxidative damage.
Conclusions:
- The interplay between NRs and Nrf2 presents a promising avenue for therapeutic intervention in liver diseases.
- Understanding NR modulation of oxidative stress can guide the repurposing of existing drugs to combat ROS.
- Targeting NRs offers a potential strategy to ameliorate liver injury caused by various environmental and chemical insults.
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