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Environmental contaminants modulate transport activity of zebrafish organic anion transporters Oat1 and Oat3.
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2020-03-09 , DOI: 10.1016/j.cbpc.2020.108742
Jelena Dragojević 1 , Petra Marić 1 , Jovica Lončar 1 , Marta Popović 1 , Ivan Mihaljević 1 , Tvrtko Smital 1
Affiliation  

Organic anion transporters (OATs) are transmembrane proteins which belong to SLC22 subfamily. They are responsible for the uptake of various endo- and xenobiotics into the cells of different organs and tissues. Following our previous work on characterization of zebrafish Oat1 and Oat3, in this study we analyzed interaction of various classes of environmental contaminants with these membrane transporters using the transport activity assay with HEK293 Flp-In cell line stably overexpressing zebrafish Oat1 and Oat3, respectively. Based on the initial screening of a series of 36 environmental contaminants on their ability to interact with zebrafish Oat1 and Oat3, the most potent interactors were selected, their IC50 values calculated and type of interaction determined. Finally, to further confirm the type of interaction and initially evaluate their toxic potential, the cytotoxicity assays were performed. Broad ligand selectivity and similarity of zebrafish Oat1 and Oat3 with mammalian orthologs was confirmed and potent interactors among environmental contaminants identified.

中文翻译:

环境污染物调节斑马鱼有机阴离子转运蛋白Oat1和Oat3的转运活性。

有机阴离子转运蛋白(OAT)是跨膜蛋白,属于SLC22家族。它们负责将各种内源性和异源性生物吸收到不同器官和组织的细胞中。在我们先前对斑马鱼Oat1和Oat3进行表征的工作之后,在本研究中,我们分别使用稳定过表达斑马鱼Oat1和Oat3的HEK293 Flp-In细胞系的转运活性分析法,分析了各种环境污染物与这些膜转运蛋白的相互作用。根据对36种环境污染物与斑马鱼Oat1和Oat3相互作用的能力的初步筛选,选择了最有效的相互作用剂,计算了它们的IC50值并确定了相互作用类型。最后,为了进一步确认相互作用的类型并初步评估其毒性潜力,进行了细胞毒性试验。斑马鱼Oat1和Oat3与哺乳动物的直系同源物具有广泛的配体选择性和相似性,并确定了环境污染物之间的有效相互作用者。
更新日期:2020-03-10
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