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芳烃受体(AHR)和细胞色素P450 1A(CYP1A)的表达将历史污染事件与美国短吻鳄现今的发育影响联系起来。

AHR and CYP1A expression link historical contamination events to modern day developmental effects in the American alligator.

作者信息

Hale Matthew D, Galligan Thomas M, Rainwater Thomas R, Moore Brandon C, Wilkinson Philip M, Guillette Louis J, Parrott Benjamin B

机构信息

Savannah River Ecology Laboratory, P.O. Drawer E, Aiken, SC 29802, United States; Odum School of Ecology, University of Georgia, Athens, GA 30602, United States.

Marine Biomedicine and Environmental Sciences Program, Hollings Marine Laboratory and the Medical University of South Carolina, Charleston, SC 29412, United States.

出版信息

Environ Pollut. 2017 Nov;230:1050-1061. doi: 10.1016/j.envpol.2017.07.065. Epub 2017 Aug 10.

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today. Little is known regarding the effects that long-term chronic exposures to dioxin or dioxin-like compounds might have on the development and subsequent health of offspring from exposed individuals, nor is much known regarding AHR expression in reptilians. Here, we characterize AHR and CYP1A gene expression in embryonic and juvenile specimen of a long-lived, apex predator, the American alligator (Alligator mississippiensis), and investigate variation in gene expression profiles in offspring collected from sites conveying differential exposures to environmental contaminants. Both age- and tissue-dependent patterning of AHR isoform expression are detected. We characterize two downstream transcriptional targets of the AHR, CYP1A1 and CYP1A2, and describe conserved elements of their genomic architecture. When comparisons across different sites are made, hepatic expression of CYP1A2, a direct target of the AHR, appears elevated in embryos from a site associated with a dioxin point source and previously characterized PCB contamination. Elevated CYP1A2 expression is not persistent, as site-specific variation was absent in juveniles originating from field-collected eggs but reared under lab conditions. Our results illustrate the patterning of AHR gene expression in a long-lived environmental model species, and indicate a potential contemporary influence of historical contamination. This research presents a novel opportunity to link contamination events to critical genetic pathways during embryonic development, and carries significant potential to inform our understanding of potential health effects in wildlife and humans.

摘要

芳基烃受体(AHR)是一种配体激活的转录因子,它启动一个转录途径,负责CYP1A亚家族成员的表达,而CYP1A亚家族成员是外源性化合物代谢的关键。有毒的平面卤代芳烃,包括二恶英和多氯联苯,能够激活AHR。在美国进行严格监管后,环境中二恶英和多氯联苯的输入已大幅减少,但它们仍存在于环境中,如今接触这些物质的情况依然存在。关于长期慢性接触二恶英或二恶英类化合物可能对接触者后代的发育及后续健康产生的影响,人们了解甚少,对于爬行动物中AHR的表达情况也所知不多。在此,我们对一种长寿的顶级食肉动物——美国短吻鳄(密西西比鳄)的胚胎和幼年样本中的AHR和CYP1A基因表达进行了表征,并研究了从不同环境污染物接触水平的地点收集的后代中基因表达谱的差异。我们检测到了AHR异构体表达的年龄和组织依赖性模式。我们对AHR的两个下游转录靶点CYP1A1和CYP1A2进行了表征,并描述了它们基因组结构的保守元件。当对不同地点进行比较时,作为AHR直接靶点的CYP1A2在肝脏中的表达,在一个与二恶英点源及先前已表征的多氯联苯污染相关的地点的胚胎中似乎有所升高。CYP1A2表达升高的情况并不持续,因为来自野外采集的卵但在实验室条件下饲养的幼年个体中不存在地点特异性差异。我们的结果说明了AHR基因在一个长寿的环境模型物种中的表达模式,并表明了历史污染的潜在当代影响。这项研究提供了一个新的机会,将污染事件与胚胎发育过程中的关键遗传途径联系起来,并具有极大潜力增进我们对野生动物和人类潜在健康影响的理解。

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