UZH-Logo

Maintenance Infos

Oxygen- and dioxin-regulated gene expression in mouse hepatoma cells.


Gassmann, M; Kvietikova, I; Rolfs, A; Wenger, R H (1997). Oxygen- and dioxin-regulated gene expression in mouse hepatoma cells. Kidney International, 51(2):567-574.

Abstract

The discovery that the oxygen-regulated transcription factor HIF-1 alpha and the dioxin receptor AhR share the common heterodimerization partner ARNT (HIF-1 beta) raised the question whether a cross-talk between oxygen and dioxin signal transduction pathways exists. To answer this question we investigated an ARNT-deficient mutant cell line (Hepa1C4), which has lost its capability of responding to dioxin. The results demonstrate that the presence of ARNT is indispensable for hypoxia-inducible HIF-1 DNA binding as well as for oxygen-regulated reporter gene activity mediated by the EPO 3' hypoxia response element (HRE). Hypoxic induction of the vascular endothelial growth factor (VEGF) gene, however, was only partially abrogated in Hepa1C4 cells, suggesting that HIF-1-independent oxygen signaling pathways might exist. We further studied HIF-1 and AhR/ARNT DNA binding activity as well as the regulation of oxygen- and xenobiotic-responsive genes by treating mouse Hepa1 hepatoma cells with hypoxia and/or the dioxin analogue ICZ. Hypoxia-inducible VEGF expression was found to be independent of ICZ-treatment, whereas ICZ-inducible cytochrome P-450IA1 expression was slightly reduced by hypoxic treatment of the cells. Interestingly, the enhancer function of a xenobiotic response element (XRE) linked to a reporter gene was induced by hypoxia, but expression of a HRE-containing reporter gene was not affected by ICZ treatment.

Abstract

The discovery that the oxygen-regulated transcription factor HIF-1 alpha and the dioxin receptor AhR share the common heterodimerization partner ARNT (HIF-1 beta) raised the question whether a cross-talk between oxygen and dioxin signal transduction pathways exists. To answer this question we investigated an ARNT-deficient mutant cell line (Hepa1C4), which has lost its capability of responding to dioxin. The results demonstrate that the presence of ARNT is indispensable for hypoxia-inducible HIF-1 DNA binding as well as for oxygen-regulated reporter gene activity mediated by the EPO 3' hypoxia response element (HRE). Hypoxic induction of the vascular endothelial growth factor (VEGF) gene, however, was only partially abrogated in Hepa1C4 cells, suggesting that HIF-1-independent oxygen signaling pathways might exist. We further studied HIF-1 and AhR/ARNT DNA binding activity as well as the regulation of oxygen- and xenobiotic-responsive genes by treating mouse Hepa1 hepatoma cells with hypoxia and/or the dioxin analogue ICZ. Hypoxia-inducible VEGF expression was found to be independent of ICZ-treatment, whereas ICZ-inducible cytochrome P-450IA1 expression was slightly reduced by hypoxic treatment of the cells. Interestingly, the enhancer function of a xenobiotic response element (XRE) linked to a reporter gene was induced by hypoxia, but expression of a HRE-containing reporter gene was not affected by ICZ treatment.

Citations

73 citations in Web of Science®
72 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1997
Deposited On:11 Feb 2008 12:23
Last Modified:05 Apr 2016 12:18
Publisher:Nature Publishing Group
ISSN:0085-2538
Publisher DOI:https://doi.org/10.1038/ki.1997.81
PubMed ID:9027741

Download

Full text not available from this repository.
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations