|ZFIN ID: ZDB-PUB-101222-46|
Molecular targets that link dioxin exposure to toxicity phenotypes
Yoshioka, W., Peterson, R.E., and Tohyama, C.
|Source:||The Journal of steroid biochemistry and molecular biology 127(1-2): 96-101 (Journal)|
|Registered Authors:||Peterson, Richard E.|
|Keywords:||aryl hydrocarbon receptor, cyclooxygenase 2, dioxin, Sox9, toxicity|
|PubMed:||21168493 Full text @ Steroid Biochem. Mol. Biol.|
Yoshioka, W., Peterson, R.E., and Tohyama, C. (2011) Molecular targets that link dioxin exposure to toxicity phenotypes. The Journal of steroid biochemistry and molecular biology. 127(1-2):96-101.
ABSTRACTAn impressive number of studies have been performed to elucidate health effects associated with exposure to various chemicals, but the majority of results are phenomenological in nature. Our understanding of the toxicity of dioxins, a group of chemicals capable of causing toxicity at environmentally relevant levels of exposure, is no exception. Dioxins are unique compared to most chemicals that we are exposed to in the environment because they activate a highaffinity receptor, aryl hydrocarbon receptor (AhR) that was identified more than three decades ago. In recent years, several lines of experimental evidence have provided clues for opening the "black box" that contains the molecular mechanisms of dioxin action. These clues have emerged by toxicologists beginning to identify the molecular targets that link AhR signaling to tissue-specific toxicity phenotypes. Dioxin toxicity phenotypes for which downstream molecular targets have begun to be elucidated are observed in developmental or tissue regeneration processes, and include impaired prostate development and hydronephrosis in mouse fetuses and pups, reduced midbrain blood flow and jaw malformation in zebrafish embryos, and impaired fin regeneration in larval and adult zebrafish. Significant progress in identifying molecular targets for dioxin-induced hepatotoxicity in adult mice also has occurred.Misregulation of AhR downstream pathways, such as conversion of arachidonic acid to prostanoids via cyclooxygenase-2, and altered Wnt/β-catenin signaling downregulating Sox9, and signaling by receptors for inflammatory cytokines have been implicated in tissue-specific endpoints of dioxin toxicity. These findings may not only begin to clarify the molecular targets of dioxin action but shed light on new molecular events associated with development and disease.
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