ArticleToxicological sciences : an official journal of the Society of Toxicology2008
Induction of hepatic glutathione S-transferases in male mice by prototypes of various classes of microsomal enzyme inducers.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 70 citations in OpenAlex.
- Review
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- Benzo[ a]pyrene Induction of Glutathione S-Transferases: An Activity-Based Protein Profiling Investigation.Chemical research in toxicology · 2019Article
- Chemical Activation of the Constitutive Androstane Receptor Leads to Activation of Oxidant-Induced Nrf2.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Age-associated changes in GSH S-transferase gene/proteins in livers of rats.Redox report : communications in free radical research · 2018Article
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- RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.Biochimica et biophysica acta · 2016Article
- Regulation of Hepatic Drug-Metabolizing Enzymes in Germ-Free Mice by Conventionalization and Probiotics.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy.Frontiers in pharmacology · 2016Article
- Regulation of Drug Disposition Gene Expression in Pregnant Mice with Car Receptor Activation.Nuclear receptor research · 2016Article
- Adaptive hepatic and intestinal alterations in mice after deletion of NADPH-cytochrome P450 Oxidoreductase (Cpr) in hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Genetic or pharmacologic activation of Nrf2 signaling fails to protect against aflatoxin genotoxicity in hypersensitive GSTA3 knockout mice.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- A targeted in vivo SILAC approach for quantification of drug metabolism enzymes: regulation by the constitutive androstane receptor.Journal of proteome research · 2014Article
- Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway.Brain and behavior · 2013Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
The underlying need for glutathione S-transferase (Gst) induction is thought to be an adaptive response to chemical stress within the cell. Classical microsomal enzyme inducers (MEIs) increase the expression of biotransformation enzymes (phase I and II) and transporters through transcription factors, such as the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPAR) alpha, and nuclear factor erythroid-derived 2-related factor 2 (Nrf2). The effects of MEIs on the induction of hepatic Gsts in mice have not been comprehensively characterized. The purpose of this study was to determine the effects of 15 MEIs on the mRNA expression of 19 mouse Gsts. Male C57BL/6 mice were treated with three different activators each for AhR, CAR, PXR, PPARalpha, and Nrf2. In general, the Gsts are readily induced. All five transcription factors appear to play a role in Gst induction. The Nrf2 activators induced most Gsts (10), followed by the CAR, PXR, and PPARalpha activators (6-7), whereas the AhR ligands induced the least (1). Clofibrate, a PPARalpha agonist, induced most of the Gsts; however, all three PPARalpha agonists decreased Gstp1/2 mRNA. None of the 15 inducers was able to increase or only minimally increased eight of the Gsts (Gsta3, Gstk1, Gstm6, Gsto1, Gstp1/2, Gstt3, Gstz1, and MGst1). Thus, the protection afforded by a ligand for one of these transcription factors will depend on the activator, as well as which Gst that detoxifies the chemicals of interest.
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