journal.pone.0015382.pdf (2.85 MB)
Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor
journal contribution
posted on 2023-06-07, 22:34 authored by Miguel Angel Céspedes, Maximo Ibo Galindo, Juan Pablo CousoThe Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function.
History
Publication status
- Published
File Version
- Published version
Journal
PLoS ONEISSN
1932-6203External DOI
Issue
11Volume
5Department affiliated with
- Biochemistry Publications
Notes
Article Number: e15382Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-11-16Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC