Ah Receptor Signaling Controls the Expression of Cardiac Development and Homeostasis Genes.

Autor:	Carreira VS; Department of Environmental Health and Center for Environmental Genetics and., Fan Y; Department of Environmental Health and Center for Environmental Genetics and., Wang Q; Department of Environmental Health and Center for Environmental Genetics and., Zhang X; Department of Environmental Health and Center for Environmental Genetics and., Kurita H; Department of Environmental Health and Center for Environmental Genetics and., Ko CI; Department of Environmental Health and Center for Environmental Genetics and., Naticchioni M; Department of Internal Medicine, Cardiology Division, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267., Jiang M; Department of Internal Medicine, Cardiology Division, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267., Koch S; Department of Internal Medicine, Cardiology Division, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267., Medvedovic M; Department of Environmental Health and Center for Environmental Genetics and., Xia Y; Department of Environmental Health and Center for Environmental Genetics and., Rubinstein J; Department of Internal Medicine, Cardiology Division, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267., Puga A; Department of Environmental Health and Center for Environmental Genetics and alvaro.puga@uc.edu.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2015 Oct; Vol. 147 (2), pp. 425-35. Date of Electronic Publication: 2015 Jul 02.
DOI:	10.1093/toxsci/kfv138
Abstrakt:	Congenital heart disease (CHD) is the most common congenital abnormality and one of the leading causes of newborn death throughout the world. Despite much emerging scientific information, the precise etiology of this disease remains elusive. Here, we show that the aryl hydrocarbon receptor (AHR) regulates the expression of crucial cardiogenesis genes and that interference with endogenous AHR functions, either by gene ablation or by agonist exposure during early development, causes overlapping structural and functional cardiac abnormalities that lead to altered fetal heart physiology, including higher heart rates, right and left ventricle dilation, higher stroke volume, and reduced ejection fraction. With striking similarity between AHR knockout (Ahr(-/-)) and agonist-exposed wild type (Ahr(+/+)) embryos, in utero disruption of endogenous AHR functions converge into dysregulation of molecular mechanisms needed for attainment and maintenance of cardiac differentiation, including the pivotal signals regulated by the cardiogenic transcription factor NKH2.5, energy balance via oxidative phosphorylation and TCA cycle and global mitochondrial function and homeostasis. Our findings suggest that AHR signaling in the developing mammalian heart is central to the regulation of pathways crucial for cellular metabolism, cardiogenesis, and cardiac function, which are potential targets of environmental factors associated with CHD. (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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