Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

Céspedes, Miguel Angel, Galindo, Maximo Ibo and Couso, Juan Pablo (2010) Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor. PLoS ONE, 5 (11). ISSN 1932-6203

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

The 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.

Item Type: Article
Additional Information: Article Number: e15382
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Miguel Cespedes
Date Deposited: 06 Feb 2012 19:19
Last Modified: 07 Mar 2017 04:49
URI: http://sro.sussex.ac.uk/id/eprint/20081

View download statistics for this item

📧 Request an update