University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland; Swiss Federal Institute of Technology Zürich (ETH Zürich), Institute of Biogeochemistry and Pollution Dynamics, Environmental Systems Science, 8092 Zürich, Switzerland.
Aquat Toxicol. 2014 May;150:93-102. doi: 10.1016/j.aquatox.2014.02.019. Epub 2014 Mar 6.
UDP-Glucuronosyltransferases (Ugts) are phase II biotransformation enzymes that glucuronidate numerous endogenous and xenobiotic substrates. Based on the reported zebrafish Ugt gene repertoire, primers for the Ugt1a and Ugt1b family and for individual Ugt5a1, Ugt5a3, Ugt5a4, Ugt5a5, Ugt5c2 and Ugt5c3 were designed and applied in RT-qPCR analyses. Transcriptional expression profiles of these Ugts were analyzed in intestine, liver, gonad and brain of female and male adult zebrafish and at different embryonic developmental stages. We found tissue-, sex- and developmental-specific expression patterns for all isoforms. Throughout all tissues, the most abundant Ugts were Ugt1a, Ugt1b, Ugt5a1 and Ugt5a3. Expression during embryonic development was assessed between 24 and 120 hpf. Ugts showed a development-dependent expression. The pattern of Ugt1a, Ugt1b, Ugt5a1, Ugt5a3 and Ugt5a4 were similar with highest expression at 24 hpf followed by a decrease and rebound increase up to 120 hpf. To analyze for transcriptional regulation of Ugts by the arylhydrocarbon receptor (ahr2), zebrafish eleuthero-embryos were exposed to 5, 25 and 50μg/L benzo(a)pyrene (BaP), a model ahr2 regulator for cyp1a. Besides transcriptional induction of ahr2 and cyp1a, BaP produced a significant induction of Ugt1a, Ugt5a1, Ugt5a3 and Ugt5a5 as well as a down-regulation of Ugt1b. These data demonstrate the link between ahr2 signalling and transcriptional expression of Ugt genes. This is the first study showing transcriptional expression of eight different Ugts in tissues and during embryonic development and offers new perspectives on the involvement of Ugts in fish xenobiotic metabolism.
尿苷二磷酸葡萄糖醛酸转移酶（UGTs）是 II 相生物转化酶，可使许多内源性和外源性底物葡萄糖醛酸化。基于已报道的斑马鱼 Ugt 基因库，设计了用于 Ugt1a 和 Ugt1b 家族以及个别 Ugt5a1、Ugt5a3、Ugt5a4、Ugt5a5、Ugt5c2 和 Ugt5c3 的引物，并应用于 RT-qPCR 分析。分析了这些 Ugt 在雌性和雄性成年斑马鱼的肠、肝、性腺和脑以及不同胚胎发育阶段的转录表达谱。我们发现所有同工酶均具有组织特异性、性别特异性和发育特异性表达模式。在所有组织中，最丰富的 Ugt 是 Ugt1a、Ugt1b、Ugt5a1 和 Ugt5a3。在胚胎发育期间，从 24 到 120 hpf 进行了评估。UGTs 的表达具有发育依赖性。Ugt1a、Ugt1b、Ugt5a1、Ugt5a3 和 Ugt5a4 的表达模式相似，在 24 hpf 时表达最高，随后下降，到 120 hpf 时又反弹增加。为了分析芳基烃受体（ahr2）对 Ugt 的转录调控，将斑马鱼 eleuthero 胚胎暴露于 5、25 和 50μg/L 苯并（a）芘（BaP），BaP 是一种用于 Cyp1a 的模型 ahr2 调节剂。除了 ahr2 和 Cyp1a 的转录诱导外，BaP 还显著诱导了 Ugt1a、Ugt5a1、Ugt5a3 和 Ugt5a5 的表达，并下调了 Ugt1b 的表达。这些数据表明 ahr2 信号与 Ugt 基因的转录表达之间存在联系。这是第一项在组织和胚胎发育过程中研究八种不同 Ugt 的转录表达的研究，并为 Ugt 在鱼类外源物代谢中的作用提供了新的视角。
