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A temporal high-resolution investigation of the Ah-receptor pathway during early development of zebrafish (Danio rerio)
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2018-09-15 , DOI: 10.1016/j.aquatox.2018.09.007
Henriette Meyer-Alert , Kim Ladermann , Maria Larsson , Sabrina Schiwy , Henner Hollert , Steffen H. Keiter

In order to contribute to a comprehensive understanding of the regulating mechanisms of the aryl-hydrocarbon-receptor (AHR) in zebrafish embryos, we aimed to elucidate the interaction of proteins taking part in this signaling pathway during early development of the zebrafish (Danio rerio) after chemical exposure. We managed to illustrate initial transcription processes of the implemented proteins after exposure to two environmentally relevant chemicals: polychlorinated biphenyl 126 (PCB126) and β-Naphthoflavone (BNF). Using qPCR, we quantified mRNA every 4 h until 118 h post fertilization and found the expression of biotransformation enzymes (cyp1 family) and the repressor of the AHR (ahr-r) to be dependent on the duration of chemical exposure and the biodegradability of the compounds. PCB126 induced persistently increased amounts of transcripts as it is not metabolized, whereas activation by BNF was limited to the initial period of exposure. We did not find a clear relation between the amount of transcripts and activity of the induced CYP-proteins, so posttranscriptional mechanisms are likely to regulate biotransformation of BNF. With regard to zebrafish embryos and their application in risk assessment of hazardous chemicals, our examination of the AHR pathway especially supports the relevance of the time point or period of exposure that is used for bioanalytical investigations and consideration of chemical properties determining biodegradability.



中文翻译:

斑马鱼的早期发育过程中阿受体途径的时间高分辨率调查(斑马鱼

为了有助于全面了解斑马鱼胚胎中芳基-碳氢化合物受体(AHR)的调节机制,我们旨在阐明斑马鱼早期发育过程中参与该信号通路的蛋白质之间的相互作用(Danio rerio)化学暴露后。我们设法说明了在暴露于两种与环境有关的化学物质后的蛋白质的初始转录过程:多氯联苯126(PCB126)和β-萘黄酮(BNF)。使用qPCR,我们每4小时对受精后直至118 h的mRNA进行定量,发现生物转化酶(cyp1家族)的表达和AHR的阻遏物(ahr -r)取决于化合物的化学暴露时间和生物降解能力。PCB126诱导转录物的量持续增加,因为它不被代谢,而BNF的激活仅限于暴露的初期。我们没有发现转录本的数量和诱导的CYP蛋白活性之间的明确关系,因此转录后机制可能会调节BNF的生物转化。关于斑马鱼胚胎及其在危险化学品风险评估中的应用,我们对AHR途径的检查特别支持了用于生物分析研究和考虑化学性质以确定可生物降解性的接触时间点或时间段的相关性。

更新日期:2018-09-15
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