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| Publications [#170811] of Richard T. Di Giulio
Papers Published
- Fleming, Carrie R. and Billiard, Sonya M. and Di Giulio, Richard T., Hypoxia inhibits induction of aryl hydrocarbon receptor activity in topminnow hepatocarcinoma cells in an ARNT-dependent manner,
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, vol. 150 no. 3
(September, 2009),
pp. 383-389, ISSN 1532-0456 [doi]
(last updated on 2010/01/26)
Abstract:
Hypoxic events often occur in waters contaminated with toxic chemicals, including agonists of the aryl hydrocarbon receptor (AhR). HIF-1 alpha, 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 0\% 02) 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-1 alpha is able to sequester ARNT from AhR and limit the activity of the AhR pathway, but suggests that the converse is not true. (C) 2009 Elsevier Inc. All rights reserved.
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