engleski

First characterization of Multidrug and Toxin Extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio)

Multidrug and toxin extrusion (MATE) proteins from the solute carrier superfamily (SLC) are involved in the extrusion of endo- and xenobiotics across the plasma membrane, similar to the ATP-binding cassette (ABC) transporters, but in ATP non-dependent manner since they use proton gradient as the driving force for the efflux. MATEs are conserved from bacteria to mammals with differing number of genes within groups. In humans, three MATEs have been found (MATE1, 2, 2k), whereas in zebrafish (Danio rerio) we have found six members annotated as DrMate 3-8. We present first insight into the zebrafish (Danio rerio) Mate proteins based on the phylogenetic analysis, tissue expression profiling and functional characterization. Phylogenetic analysis revealed six Mates in teleost fish which form a distinct cluster separated from the tetrapod MATEs. Tissue expression analysis showed high expression of zebrafish Mates in toxicologically important tissues, kidney and liver, as well as in testes. We have determined transporter kinetic parameters for the uptake of 6 fluorescent dyes out of which 4′, 6-diamidino-2-phenylindole (DAPI) was selected as a dye of choice for subsequent testing of more than 20 selected interactors of mammalian MATEs. Inhibition constants (Ki) were determined for more than 10 physiological and xenobiotic compounds including hormones, bile salts, drugs and pesticides. To summarize, we have characterised zebrafish Mate transporters on the bioinformatical, expressional and functional level giving first insight into fish efflux transporters from SLC superfamily.

Multidrug and Toxin Extrusion (MATE/SLC47) proteins ; zebrafish

nije evidentirano