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Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis

Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
Department of Anesthesiology, Institute of Translation Medicine, the First People's Hospital of Chenzhou, Chenzhou 423000, China
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(7), 11700-11712;
Received: 22 April 2014 / Revised: 13 June 2014 / Accepted: 17 June 2014 / Published: 1 July 2014
(This article belongs to the Special Issue Mechanisms of Toxicity of Dioxins and Related Compounds)
The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock. This intrinsic molecular clock is pivotal for maintenance of synchronized homeostasis between the individual organism and the external environment to allow coordinated rhythmic physiological and behavioral function. Aryl hydrocarbon receptor (AhR) is a master regulator of dioxin-mediated toxic effects, and is, therefore, critical in maintaining adaptive responses through regulating the expression of phase I/II drug metabolism enzymes. AhR expression is robustly rhythmic, and physiological cross-talk between AhR signaling and circadian rhythms has been established. Increasing evidence raises a compelling argument that disruption of endogenous circadian rhythms contributes to the development of disease, including sleep disorders, metabolic disorders and cancers. Similarly, exposure to environmental pollutants through air, water and food, is increasingly cited as contributory to these same problems. Thus, a better understanding of interactions between AhR signaling and the circadian clock regulatory network can provide critical new insights into environmentally regulated disease processes. This review highlights recent advances in the understanding of the reciprocal interactions between dioxin-mediated AhR signaling and the circadian clock including how these pathways relate to health and disease, with emphasis on the control of metabolic function. View Full-Text
Keywords: dioxin; aryl hydrocarbon receptor; circadian clock dioxin; aryl hydrocarbon receptor; circadian clock
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Wang, C.; Zhang, Z.-M.; Xu, C.-X.; Tischkau, S.A. Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis. Int. J. Mol. Sci. 2014, 15, 11700-11712.

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