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Interaction of environmental contaminants with zebrafish (Danio rerio) multidrug and toxin extrusion protein 7 (Mate7/Slc47a7)

Lončar, Jovica; Smital, Tvrtko (2018) Interaction of environmental contaminants with zebrafish (Danio rerio) multidrug and toxin extrusion protein 7 (Mate7/Slc47a7). Aquatic Toxicology, 205 . pp. 193-203. ISSN 0166-445X

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Abstract

Zebrafish Mate7 belongs to solute carrier protein superfamily and specifically to subfamily of multidrug and toxin extruders. It is co-orthologous to mammalian Mates, and is ubiquitously expressed in zebrafish tissues with the highest expression in kidney. It has been shown to interact with both endogenous (steroid hormones) and xenobiotic compounds (pharmaceuticals), implying a role in efflux of toxic compounds. The objective of our study was to analyse interaction of environmental contaminants with zebrafish Mate7 using a newly developed high throughput screening (HTS) Mate7 assay. A full-length zebrafish mate7 sequence was obtained from zebrafish cDNA originating from male kidney, and a stable expression of Mate7 in genetically engineered HEK293 Flp-In cells was achieved. Stable Mate7 transfectants were then used for development and optimization of a new HTS cellular uptake protocol, with DAPI and ASP+as model fluorescent substrates. The developed assay was used for identifying zebrafish Mate 7 interactors and discerning the type of interaction. A series of 89 diverse environmental contaminants, including industrial chemicals, pesticides, and pharmaceuticals, was tested and highly effective Mate7 interactors were identified in all of the aforementioned groups. Some of the inhibitors identified could be of environmental concern because they may potentially impair Mate7 efflux function, lowering the fish defence capacity against environmental contaminants, or interfering with transport of yet unidentified physiological substrates. In addition, we found significant differences between zebrafish Mate7 and mammalian Mates’ substrate preferences, a finding that should be taken into consideration when using zebrafish as a model organism in toxicokinetic studies.

Item Type: Article
Additional Information: This work was supported by the Croatian National Science Foundation (Project No. 4806), the SCOPES programme joint research project granted by the Swiss National Science Foundation (SNSF) (Grant No. SCOPES -IZ73ZO_152274/1), and by STIM - REI, a project funded by European Union from European Structural and Investment Funds 2014-2020, Contract Number: KK.01.1.1.01.0003.
Uncontrolled Keywords: Mate7; environmental contaminants; high throughput screening assay; HEK293 flp-in cells
Subjects: NATURAL SCIENCES
NATURAL SCIENCES > Biology > Zoology
NATURAL SCIENCES > Biology > General Biology
Divisions: Division for Marine and Enviromental Research
Projects:
Project titleProject leaderProject codeProject type
Identifikacija i funkcionalna karakterizacija (eko)toksikološki važnih polispecifičnih membranskih transportnih proteina u zebrici (Danio rerio)-TRANS-ZEBRATOXTvrtko SmitalIP-2013-11-4806HRZZ
Identification and characterization of cyanobacterial toxins based on their interaction with basic cellular detoxification systems in zebrafish (Danio rerio) and zooplankton Daphnia magnaTvrtko SmitalSCOPES - IZ73ZO_152274/1SNSF
Ecotoxicological characterization of biologically active substances and complex marine environment samples - Project within the Centre for Excellence for Science and Technology – Integration of Mediterranean Region (ZCI-STIM; https://stim.unist.hr/hr/)Tvrtko SmitalKK.01.1.1.01EU Reg. Development Fund
Depositing User: Tvrtko Smital
Date Deposited: 22 Nov 2019 12:19
Last Modified: 22 Nov 2019 15:50
URI: http://fulir.irb.hr/id/eprint/5114
DOI: https://doi.org/10.1016/j.aquatox.2018.10.016

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