Environmental contaminants modulate transport activity of zebrafish organic anion transporters Oat1 and Oat3

Dragojević, Jelena; Marić, Petra; Lončar, Jovica; Popović, Marta; Mihaljević, Ivan; Smital, Tvrtko (2020) Environmental contaminants modulate transport activity of zebrafish organic anion transporters Oat1 and Oat3. Comparative Biochemistry and Physiology - Part C: Toxicology and Pharmacology, 231 . ISSN 1532-0456

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Abstract

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.

Item Type:	Article
Additional Information:	This research described here was financially supported by Project No. 4806 granted by the Croatian National Science Foundation, the SCOPES programme joint research project granted by the Swiss National Science Foundation (SNSF) (Grant No. SCOPES - IZ73ZO_152274/1), and by the project STIM -REI, Contract Number: KK.01.1.1.01.0003, a project funded by the European Union through the European Regional Development Fund - the Operational Programme Competitiveness and Cohesion 2014-2020 (KK.01.1.1.01).
Uncontrolled Keywords:	Oat1 and Oat3 transporters ; zebrafish ; stable transfectants ; environmental contaminants ; interaction screening ; cytotoxicity
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division for Marine and Enviromental Research
Projects:	Project title Project leader Project code Project type UNSPECIFIED UNSPECIFIED SCOPES - IZ73ZO_152274/1 UNSPECIFIED UNSPECIFIED UNSPECIFIED KK.01.1.1.01 UNSPECIFIED Identifikacija i funkcionalna karakterizacija (eko)toksikološki važnih polispecifičnih membranskih transportnih proteina u zebrici (Danio rerio)-TRANS-ZEBRATOX Tvrtko Smital IP-2013-11-4806 HRZZ
Depositing User:	Tvrtko Smital
Date Deposited:	07 May 2020 05:59
URI:	http://fulir.irb.hr/id/eprint/5744
DOI:	10.1016/j.cbpc.2020.108742

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