Nuclear Receptor‐Mediated Regulation of Phase II Conjugating Enzymes

Barbier, Oliver

doi:10.1002/9780470409107.ch3

Cited by 3 publications

(1 citation statement)

References 232 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over‐production of CncC and Maf will give rise to wide influences on gene expression, especially enhancing the expression of multiple detoxification genes under the control of CncC/Maf binding element . In HZ16 of S. exigua at least three SeGST genes are found to be the target genes of CncC/Maf and belong to the Nrf2 battery . These three SeGST proteins can directly eliminate the multiple insecticides tested in this study.…”

Section: Discussionmentioning

confidence: 99%

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Huang

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

BACKGROUND: Glutathione S-transferases (GSTs) are a superfamily of multifunctional dimeric proteins existing in both prokaryotic and eukaryotic organisms. They are involved in the detoxification of both endogenous and exogenous electrophiles, including insecticides. However, the molecular mechanisms underlying the regulation of GST genes in insects are poorly understood. RESULTS:We first identified at least three GST genes involved in resistance to the insecticides chlorpyrifos and cypermethrin. Analysis of upstream sequences revealed that three GSTs (SeGSTo2, SeGSTe6 and SeGSTd3) harbor the same cap 'n' collar C/muscle aponeurosis fibromatosis (CncC/Maf) binding site, and SeGSTo2 and SeGSTe6 contain the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) binding site. Luciferase reporter assay showed co-transfection of reporter plasmid containing the SeGSTe6 promoter with CncC and/or Maf expressing constructs significantly boosted transcription. Similarly, AhR and/or ARNT expressing constructs also significantly increased the promoter activities. The co-transfection of mutated reporter plasmid with CncC/Maf or AhR/ARNT did not increase transcription activity anymore. Constitutive over-expression of CncC, Maf and AhR was also found in the HZ16 strain, which might be the molecular mechanism for up-regulated expression of multiple detoxification genes conferring resistance to insecticides. CONCLUSION: These results suggest that CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GST genes involved in insecticide resistance in Spodoptera exigua.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Huang

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

show abstract

Regulation of endobiotics glucuronidation by ligand-activated transcription factors: physiological function and therapeutic potential

Verreault

Kaeding

Caron

et al. 2009

Drug Metabolism Reviews

View full text Add to dashboard Cite

Recent progresses in molecular pharmacology approaches have allowed the identification and characterization of a series of nuclear receptors (NR) which efficiently control the level UDP-glucuronosyltransferase (UGT) genes expression. These regulatory processes ensure optimized UGT expression in response to specific endogenous and/or exogenous stimuli. Interestingly, numerous endogenous activators of these NRs are conjugated by the UGT enzymes they regulate. In such a case, the NR-dependent regulation of UGT genes corresponds to a feedforward/feedback mechanism by which a bioactive molecule controls its own concentrations. In the present review, we will discuss i) how bilirubin reduces its circulating levels by activating AhR in the liver; ii) how bile acids modulate their hepatic glucuronidation via PXR- and FXR-dependent processes in enterohepatic tissues; and iii) how androgens inhibit their cellular metabolism in prostate cancer cells through an AR-dependent mechanism. Subsequently, with further discussion of the same examples (bilirubin and bile acids), we will illustrate how NR-dependent regulation of UGT enzymes may contribute to the beneficial effects of pharmacological activators of nuclear receptors, such as CAR and PPARa.

show abstract

Nuclear receptors and endobiotics glucuronidation: the good, the bad, and the UGT

Bigo

Caron

Dallaire-Theroux

et al. 2013

Drug Metabolism Reviews

View full text Add to dashboard Cite

The recent progresses in molecular biology and pharmacology approaches allowed the characterization of a series of nuclear receptors (NRs) as efficient regulators of uridine diphosphate glucuronosyltransferase (UGT) genes activity. These regulatory processes ensure an optimized UGT expression in response to specific endo- and/or exogenous stimuli. Many of these NRs are activated by endobiotics that also are substrates for UGTs. Thus, by activating their receptors, these endogenous substances control their own conjugation, leading to the concept that glucuronidation is an important part of feed-forward/feedback mechanisms by which bioactive molecules control their own concentrations. On the other hand, numerous studies have established the pharmacological relevance of NR-UGT regulatory pathways in the response to therapeutic ligands. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of the NR regulation of the expression and activity of endobiotics-conjugating UGT enzymes. Selected examples will illustrate how the organism profits from the feed-forward/feedback mechanisms involving NR-UGT pathways, but also how such regulatory processes are involved in the initiation and/or progression of several pathological situations. Finally, we will discuss how the present pharmacopeia involves NR-dependent regulation of endobiotics glucuronidation, and whether the unexploited NR-UGT axes could serve as pharmacological targets for novel therapeutics to restore endobiotics homeostasis.

show abstract

Nuclear Receptor‐Mediated Regulation of Phase II Conjugating Enzymes

Cited by 3 publications

References 232 publications

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Regulation of endobiotics glucuronidation by ligand-activated transcription factors: physiological function and therapeutic potential

Nuclear receptors and endobiotics glucuronidation: the good, the bad, and the UGT

Contact Info

Product

Resources

About