Journal article
PCB 126 PERTURBS HYPOXIA-INDUCED HIF-1α ACTIVITY AND GLUCOSE CONSUMPTION IN HUMAN HEPG2 CELLS
Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, Vol.66(8), pp.377-382
10/2014
DOI: 10.1016/j.etp.2014.05.005
PMCID: PMC4143452
PMID: 24916446
Abstract
Aerobic organisms strongly depend on the availability of oxygen for respiration and countless other metabolic processes to maintain cellular homeostasis. Under certain conditions, the amount of available oxygen can be limited. To support survival in environments with limited oxygen supply, hypoxia-inducible factors (HIFs) reprogram vital components of cellular metabolism. HIF-1α is an important mediator of acute and adaptive responses to hypoxic stress. Interestingly, the heterodimeric partner required by HIF-1α to function as transcription factor, known as ARNT, is also an essential part of the aryl hydrocarbon receptor (AhR) transcription factor complex. Thus, via ARNT a crosstalk exists between these two pathways that might affect HIF-1α-mediated processes. In this study we sought to assess the effect of the AhR agonist PCB 126 on HIF-1α activity as well as on HIF-1α-regulated targets involved in cellular metabolism in human HepG2 cells. Our results show that PCB 126 reduced HIF-1α localization to the nucleus. Furthermore, in an
in vivo
setting, rats exposed to parenteral PCB 126 also displayed reduced hepatocyte nuclear localization of HIF-1α. Additionally, HepG2 cells exposed to PCB126 displayed reduced hypoxia-regulated HRE-luciferase reporter gene expression as well as a reduction in glucose consumption in conditions of hypoxia. In summary, this study reveals that HIF-1α-regulated cellular metabolic processes are negatively affected by PCB 126 which might ultimately affect adaptive responses and cell survival in hypoxic environments.
Details
- Title: Subtitle
- PCB 126 PERTURBS HYPOXIA-INDUCED HIF-1α ACTIVITY AND GLUCOSE CONSUMPTION IN HUMAN HEPG2 CELLS
- Creators
- Sabine U Vorrink - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USAEhab H Sarsour - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USAAlicia K Olivier - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USALarry W Robertson - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USAPrabhat C Goswami - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USAFrederick E Domann - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, Vol.66(8), pp.377-382
- DOI
- 10.1016/j.etp.2014.05.005
- PMID
- 24916446
- PMCID
- PMC4143452
- NLM abbreviation
- Exp Toxicol Pathol
- ISSN
- 0940-2993
- eISSN
- 1618-1433
- Grant note
- DOI: 10.13039/100000041, name: American Diabetes Association, award: #7-13-IN-12; DOI: 10.13039/100000002, name: National Institutes of Health, award: P42 ES013661-5099; DOI: 10.13039/100000054, name: National Cancer Institute of the National Institutes of Health, award: P30CA086862-8623
- Language
- English
- Date published
- 10/2014
- Academic Unit
- Occupational and Environmental Health; Pathology; Surgery; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984002351202771
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