2018
DOI: 10.1007/s00204-018-2321-x
|View full text |Cite
|
Sign up to set email alerts
|

Propiconazole is an activator of AHR and causes concentration additive effects with an established AHR ligand

Abstract: Pesticides can exert adverse effects on different target organs via the activation of nuclear receptor pathways. Hepatotoxic effects of the widely used triazole fungicide propiconazole (Pi) are generally attributed to the activation of the ligand-activated transcription factor constitutive androstane receptor (CAR) or the pregnane X receptor (PXR). We now investigated the effects of Pi on the ligand-activated transcription factor aryl hydrocarbon receptor AHR. Therefore, the effects of Pi on AHR-dependent repo… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
10
0

Year Published

2019
2019
2023
2023

Publication Types

Select...
6
1

Relationship

2
5

Authors

Journals

citations
Cited by 14 publications
(10 citation statements)
references
References 48 publications
0
10
0
Order By: Relevance
“…For human liver cells, in vitro evidence at the reporter gene, target mRNA, protein, and enzyme activity level suggests weak agonism of propiconazole at the AHR, substantiated by in silico molecular docking study results [16,26,27,31,35,37,38]. Additionally, in vitro experiments using a human AHR antagonist, AHR binding site-mutated reporter variants or AHR knockout cells mechanistically strengthen the evidence for AHR activation by propiconazole [31]. Target mRNA [5] [31,37,38] Target protein [26,31] Target enzyme activity [31,35,37] In vivo studies Target mRNA [6] [4,31,36] Target enzyme activity [36] [31,36] Similarly, in vivo rat and mouse data at the target mRNA and enzyme activity levels indirectly connect propiconazole with the activation of CAR [5,6,20,33,36,39,40] (Table 2).…”
Section: Propiconazolementioning
confidence: 90%
See 3 more Smart Citations
“…For human liver cells, in vitro evidence at the reporter gene, target mRNA, protein, and enzyme activity level suggests weak agonism of propiconazole at the AHR, substantiated by in silico molecular docking study results [16,26,27,31,35,37,38]. Additionally, in vitro experiments using a human AHR antagonist, AHR binding site-mutated reporter variants or AHR knockout cells mechanistically strengthen the evidence for AHR activation by propiconazole [31]. Target mRNA [5] [31,37,38] Target protein [26,31] Target enzyme activity [31,35,37] In vivo studies Target mRNA [6] [4,31,36] Target enzyme activity [36] [31,36] Similarly, in vivo rat and mouse data at the target mRNA and enzyme activity levels indirectly connect propiconazole with the activation of CAR [5,6,20,33,36,39,40] (Table 2).…”
Section: Propiconazolementioning
confidence: 90%
“…Especially by using specific constructs in reporter gene assays, in vitro data contribute the bulk of direct evidence for interaction of a certain azole fungicide with one of the nuclear receptors of interest. Computational approaches such as molecular docking or toxicogenomic pathway analyses have played a role in a minority of past projects to identify the nuclear receptor-interacting potential of azoles [6,[31][32][33]. As a rule, the vast majority of effects observed were receptor activation and subsequent target gene induction.…”
Section: Interactions Of Azoles With Xeno-sensing Receptorsmentioning
confidence: 99%
See 2 more Smart Citations
“…These developed models provided a clear basis towards understanding the mechanism of ligand-dependent activation of AHR via its PAS B domain. In particular, the above mentioned molecular docking and mutagenesis analyses helped in identifying and confirming the binding pocket of TCDD and other AhR modulators [46,51,54,55].…”
Section: Interaction Of the Pas B Domain With Different Ligandsmentioning
confidence: 99%