Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Hypoxia inhibits induction of aryl hydrocarbon receptor activity in topminnow hepatocarcinoma cells in an ARNT-dependent manner.

Authors: Fleming, Carrie R; Billiard, Sonya M; Di Giulio, Richard T

Published In Comp Biochem Physiol C Toxicol Pharmacol, (2009 Sep)

Abstract: Hypoxic events often occur in waters contaminated with toxic chemicals, including agonists of the aryl hydrocarbon receptor (AhR). HIF-1alpha, the mediator of cellular responses to hypoxia, shares a dimerization partner (ARNT) with AhR and reciprocal crosstalk may occur. Studies addressing AhR/hypoxia crosstalk in mammalian cells have produced contradictory results regarding whether reciprocal crosstalk actually occurs between these pathways and the role ARNT plays in this interaction. We assessed hypoxia-AhR crosstalk in fish cells (PLHC-1) treated with hypoxia (1% O(2)) or normoxia (21% O(2)) and AhR agonists (benzo[a]pyrene (BaP), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and benzo[k]fluoranthene (BkF)) with and without overexpression of ARNT. Hypoxia limited the induction of a transiently transfected AhR reporter by all three of the AhR agonists; overexpression of ARNT eliminated this effect. PCB-126 had no effect on induction of a transiently transfected hypoxia reporter. BkF caused a minor increase in basal and induced hypoxia reporter activity. BaP decreased basal and induced hypoxia reporter activity; overexpression of ARNT did not alter this effect indicating that this interference with hypoxia pathway activity occurs through an alternate mechanism. Reduced hypoxia pathway activity with BaP treatment may be the result of a metabolite. This study supports the hypothesis that HIF-1alpha is able to sequester ARNT from AhR and limit the activity of the AhR pathway, but suggests that the converse is not true.

PubMed ID: 19539049 Exiting the NIEHS site

MeSH Terms: Animals; Anoxia/metabolism*; Aryl Hydrocarbon Receptor Nuclear Translocator/physiology*; Benzo(a)pyrene/pharmacology; Carcinoma, Hepatocellular/metabolism; Cell Line, Tumor; Fundulidae/metabolism; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*; Polychlorinated Biphenyls/pharmacology; Protein Multimerization; Receptors, Aryl Hydrocarbon/biosynthesis*; Receptors, Aryl Hydrocarbon/genetics; Water Pollutants, Chemical/pharmacology

Back
to Top