Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node

Sabine U Vorrink; Frederick E Domann

doi:10.1016/j.cbi.2014.05.001

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Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node

Journal article

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Peer reviewed

Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node

Sabine U Vorrink and Frederick E Domann

Chemico-biological interactions, Vol.218, pp.82-88

07/25/2014

DOI: 10.1016/j.cbi.2014.05.001

PMCID: PMC4091760

PMID: 24824450

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Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the responses to toxic environmental chemicals such as TCDD or dioxin-like PCBs. To regulate gene expression, the AhR requires its binding partner, the aryl hydrocarbon receptor nuclear translocator (ARNT). ARNT is also required by the hypoxia-inducible factor-1α (HIF-1α), a crucial regulator of responses to conditions of reduced oxygen. The important role of ARNT in both the AhR and HIF-1α signaling pathways establishes a meaningful foundation for a possible crosstalk between these two vitally important signaling pathways. This crosstalk might lead to interference between the two signaling pathways and thus might play a role in the variety of cellular responses after exposure to AhR ligands and reduced oxygen availability. This review focuses on studies that have analyzed the effect of low oxygen environments and hypoxia-mimetic agents on AhR signaling and conversely, the effect of AhR ligands, with a special emphasis on PCBs, on HIF-1α signaling. We highlight studies that assess the role of ARNT, elucidate the mechanism of the crosstalk, and discuss the physiological implications for exposure to AhR-inducing compounds in the context of hypoxia.

Cell Hypoxia

Hypoxia-Inducible Factor 1, alpha Subunit - pharmacology

Hypoxia-Inducible Factor 1, alpha Subunit - genetics

Models, Biological

Aryl Hydrocarbon Receptor Nuclear Translocator - physiology

Signal Transduction - physiology

Aryl Hydrocarbon Receptor Nuclear Translocator - genetics

Xenobiotics - metabolism

Gene Regulatory Networks - physiology

Hypoxia-Inducible Factor 1, alpha Subunit - physiology

Receptor Cross-Talk - physiology

Details

Title: Subtitle: Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node
Creators: Sabine U Vorrink - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA
Frederick E Domann - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA. Electronic address: frederick-domann@uiowa.edu
Resource Type: Journal article
Publication Details: Chemico-biological interactions, Vol.218, pp.82-88
DOI: 10.1016/j.cbi.2014.05.001
PMID: 24824450
PMCID: PMC4091760
NLM abbreviation: Chem Biol Interact
ISSN: 0009-2797
eISSN: 1872-7786
Publisher: Ireland
Grant note: P30 ES005605 / NIEHS NIH HHS P42 ES013661-5099 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P42 ES013661-5110 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 07/25/2014
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047612302771

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