Laboratorij za molekularnu ekotoksikologiju

Laboratorij za molekularnu ekotoksikologiju

Laboratorij se bavi proučavanjem staničnih detoksifikacijskih mehanizama kod organizama vodenih ekosustava.

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LME lab

Misija – temeljna ekotoksikološka istraživanja usmjerena na razumijevanje:

●  Molekularne osnove i uloge staničnih detoksifikacijskih mehanizama u organizmima vodenih ekosistema

●  Interakcija staničnih detoksifikacijskih mehanizama sa klasičnim i novim okolišnim zagađivalima

Krajnji cilj gore navedenih temeljnih istraživanja je vrednovanje uloge staničnih detoksifikacijskih mehanizama kao ključnih sastavnica tzv. ADMETox obilježja okolišnih zagađivala. Rezultati naših istraživanja doprinijet će i poboljšanju i/ili razvoju ekotoksikoloških molekularnih biomarkera tzv. ‘ranog upozorenja’ te razvoju tzv.high-throughput alata za evaluaciju pojedinačnih okolišnih zagađivala, kao i evaluaciju kompleksnih okolišnih mješavina zagađivala.

Glavni istraživački pravci

1. Razumijevanje ekotoksikološkog značaja:

a) ABC (ATP Binding Cassette) transportnih proteina (efflux transportera)

b) SLC (Solute Carriers) transportnih proteina (uptake transportera)

2. Razvoj tzv. Effects-Directed Analyses (EDA)pristupa u svrhu identifikacije štetnih kemijskih zagađivala u okolišu.

TRANS-ZEBRATOX

Glavni istraživač / voditelj: Tvrtko Smital

Identification and functional characterization of (eco)toxicologically relevant polyspecific membrane transport proteins in zebrafish (Danio rerio)

                                                                                                                                                                                                                                                                                                                             A coordinated system of transport proteins, channels, receptors and enzymes act as cellular gatekeepers to foreign molecules, critically determining the so-called ADME-Tox (Absorption, Distribution, Metabolism, Excretion – toxicity) properties of a molecule. The polyspecific uptake and efflux transmembrane proteins are essential components of this complex cellular defense and detoxification/xenobiotic processing machinery in mammals, highly important and widely recognized in the context of pharmacology and human toxicology. However, they are scarcely investigated in non-mammalian species, and are not adequately addressed in the field of environmental toxicology. Consequently, the major goal of the proposed project is identification and detailed functional characterization of novel, (eco)toxicologically relevant uptake and efflux transport proteins that are not addressed so far in the context of environmental toxicology nor in non-mammalian species in general. Our research will be focused on selected polyspecific uptake transport proteins from the SLC21 and SLC22 (Solute Carriers) families, efflux transporters from the MATE (Multidrug and Toxic Extrusion) family, and finally, on the RLIP76 as the most recently discovered stress-responsive, multi-functional membrane protein. We will use zebrafish (Danio rerio) as a highly relevant vertebrate research model. Our methodological approach will be based on several subsequent research phases: phylogenetic and gene expression analyses; transfection studies in appropriate heterologous expression system(s); transport-activity assays; analyses of the transport mechanism and structural properties; high-throughput-screening for the identification of interactors of selected transporters among environmental contaminants; and finally, in vivo evaluation of the (eco)toxicological relevance of selected transporters using the zebrafish functional genomics tools.

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Ecotoxicological significance of ABC transport proteins in aquatic organisms

Glavni istraživač / voditelj: Tvrtko Smital

Project supported by the Croatian Ministry of Science Education and Sports

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Multixenobiotic Resistance Mechanism as a Biomarker of Environmental Quality

Glavni istraživač / voditelj: Tvrtko Smital

Project supported by the Croatian Ministry of Science and Technology, project No P0098135

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Profiling of transcript levels and functional properties of (eco)toxicologically relevant ABC transport proteins in rainbow trout (Oncorhynchus myki...

Glavni istraživač / voditelj: Tvrtko Smital

Croatia (Ministry of Science Education and Sports) – Germany (DAAD) bilateral project

više »
  • Laboratorijski prostor 126 m2;
  • Instrumenti: Tecan spektrofoto/fluorimetar (Infinite M200), PCR mašina (Biometra), Biospec Nano (Shimadzu), Bioanalizator 2100 (Agilent),  ultracentrifuga (Sorval RC28S)
  • Oprema za staničnu kulturu (sterilni kabineti, suhi i mokri inkubatori, 30-ak staničnih linija, invertni mikroskop), osnovne i napredne metode manipulacije sa staničnim kulturama
  • Izolacija primarnih stanica jetre ribe (kalifornijska pastrva)
  • Oprema za osnovne molekularno-biološke metode (PCR, PCR u stvarnom vremenu, NanoDrop, gel-elektroforeza, kloniranje, prolazne i stabilne transfekcije)
  • Imunokemijske metode: Western i ELISA
  • Enzimatske analize: aktivnost detoksifikacijskih enzima faze I i faze II 
  • In vitro i in vivo analize transportne aktivnosti membranskih proteina (supstrati obilježeni fluorescnetnim ili radioaktivnim atomima, ATPazna aktivnost)
  • Testovi citotoksičnosti, test kronične toksičnosti (AlgalTox), test genotoksičnosti (Ames test), detekcija ksenoestrogena (YES assay);
  • Zebrafish facility’; mikroinjektiranje embrija zebrice – u izradi

2005 – current 

Zaja, R., Popović, M., Lončar, J., Smital, T. (2016) Functional characterization of rainbow trout (Oncorhynchus mykiss) Abcg2a (Bcrp) transporter.Comp. Biochem. Physiol. C, 190, 15-23.

Mihaljević, I., Popović, M., Zaja, R., Smital, T. (2016) Phylogenetic, syntenic, and tissue expression analysis of slc22 genes in zebrafish (Danio rerio).BMC Genomics, 17: 626, DOI 10.1186/s12864-016-2981-y.

Lončar, J., Popović, M., Krznar, P., Zaja, R., Smital, T. (2016) The first characterization of multidrug and toxin extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio).Sci. Rep.6: 28937, DOI: 10.1038/srep28937. 

Glisic, B., Mihaljevic, I., Popovic, M., Zaja, R., Loncar, J., Fent, K., Kovacevic, R., Smital, T. (2015) Characterization of glutathione-S-transferases in zebrafish (Danio rerio).Aquat. Toxicol.158: 50-62.

Popovic, M., Zaja, R., Fent, K., Smital, T. (2014) Interaction of environmental contaminants with zebrafish uptake transporter Oatp1d1 (Slco1d1).Toxicol. Appl. Pharmacol.280: 149-158.

Ferreira, M., Santos, P., Rey-Salgueiro, L., Zaja, R., Reis-Henriques, M.A., Smital, T. (2014) The first demonstration of CYP1A and the ABC protein(s) gene expression and activity in European seabass (Dicentrarchus labrax) primary hepatocytes.Chemosphere100: 152-159.

Popovic, M., Zaja, R., Fent, K., Smital, T. (2013) Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel Organic anion transporting polypeptide.J. Biol. Chem.288: 33894–33911.

Bošnjak, I., Zaja, R., Klobučar, R.S., Sver, L., Franekić, J., Smital, T. (2013) Identification of ABC Transporter Genes in Gonad Tissue of Two Mediterranean Sea Urchin Species: Black, Arbacia lixula L., and Rocky, Paracentrotus lividus L. Bull.Environ. Contam. Toxicol.91: 415-419. 

Traven, L., Mićović, V., Vukić Lušić, D., Smital, T. (2013) The responses of the hepatosomatic index (HSI), 7-ethoxyresorufin-O-deethylase (EROD) activity and glutathione-S-transferase (GST) activity in sea bass (Dicentrarchus labrax, Linnaeus 1758) caged at a polluted site: implications for their use in environmental risk assessment.Environ Monit Assess.185: 9009-9018.

Zaja, R., Terzić, S., Senta, I., Lončar, J., Popović, M., Ahel, M., Smital, T. (2013) Identification of P-glycoprotein (P-gp, Abcb1) inhibitors in contaminated freshwater sediments.Environ. Sci. Tech.47: 4813-4821.

Smital, T., Terzić, S., Lončar, J., Senta, I., Zaja, R., Popović, M., Mikac, I., Tollefsen, K-E., Thomas, K.V., Ahel, M. (2013) Prioritisation of organic contaminants in a river basin using chemical analyses and bioassays.Environ. Sci. Poll. Res.20: 1384-1395.

Della Torre, C., Zaja, R., Loncar, J., Smital, T., Focardi, S., Corsi, I. (2012) Interaction of ABC transport proteins with toxic metals at the level of gene and transport activity in the PLHC-1 fish cell line.Chem. Biol. Interac.198: 9-17.

Reifferscheid, G., Maes, H., Allner, B., Badurova, J., Belkin, S., Blum, K., Brauer, F., Bressling, J., Domeneghetti, S., Elad, T., Flückiger-Isler, S., Grummt, H.J., Guertler, R., Hecht, A., Heringa, M., Hollert, H., Huber, S., Kramer, M., Magdeburg, A., Ratte, T., Sauerborn-Klobucar, R., Sokolowski, A., Soldan, P., Smital, T., Stalter, D., Venier, P., Ziemann, C., Zipperle, J., Buchinger, S. (2012) International round-robin study on the Ames fluctuation test. Environ. Mol. Mutag. 53: 185-197.

Zaja, R., Loncar, J., Popovic.,M., Smital, T. (2011). First characterization of fish P-glycoprotein (abcb1) substrate specificity using determinations of its ATPase activity and calcein-AM assay with PLHC-1/dox cell line. Aquat. Toxicol. 103: 53-62

Fischer, S., Loncar, J., Zaja, R., Schnell, S., Schirmer, K., Smital, T., Luckenbach, T. (2011) Constitutive mRNA expression and protein activity levels of nine ABC efflux transporters in seven permanent cell lines derived from different tissues of rainbow trout (Oncorhynchus mykiss). Aquat. Toxicol. 101: 438-446

Smital, T., Terzic, S., Zaja, R., Senta, I., Pivcevic, B., Popovic, M., Mikac, I., Tollefsen, K.E., Thomas, K.V. (2011). Assessment of toxicological profiles of the municipal wastewater effluents using chemical analyses and bioassays. Ecotox. Environ., Safe. 74 (4): 844-851.

Šrut, M., Traven, L., Štambuk, A., Kralj, S., Žaja, R., Mićović, V., Klobučar, G.I.V. (2010). Genotoxicity of marine sediments in the fish hepatoma cell line plhc-1 as assessed by the comet assay. Toxicol. in Vitro. 25 (1): 308-314

Popovic, M., Zaja, R., Loncar, J., Smital, T. (2010). A novel ABC transporter: The first insight into zebrafish (Danio rerio) Abch1. Mar. Environ. Res. 69:S1-S13.

Popovic, M. Zaja, R., Smital, T. (2009). Organic anion transporting polypeptides (OATP) in zebrafish (Danio rerio): Phylogenetic analysis and tissue distribution. CBP – Part A. 155: 327-335.

Lončar, J., Popović, M., Zaja, R., Smital, T. (2010). Gene expression analysis of the ABC efflux transporters in rainbow trout (Oncorhynchus mykiss). CBP – Part C. 151:209-215.

Dragun, Z., Erk, M., Ivanković, D., Žaja, R., Filipović Marijić, V., Raspor, B. (2009). Assessment of low-level metal contamination using the Mediterranean mussel gills as the indicator tissue. Environ. Sci. Pollut. Res. 17: 977-986.

Bošnjak, Ivana; Heim, Wesley; Smital, Tvrtko; Epel, David; Coale, Kenneth; Franekić-Čolić, Jasna; Hamdoun, Amro. Multidrug resistance associated protein transport activity mediates differences in accumulation and toxicity of inorganic and organic mercury in sea urchin embryos. //Environmental science & technology. 43 (2009) ; 8374-8380.

Zaja, R., Munić, V., Klobučar, R.S., Ambriović-Ristov, A., Smital, T. (2008). Cloning and molecular characterization of apical efflux transporters (ABCB1, ABCB11 and ABCC2) in rainbow trout (Oncorhynchus mykiss) hepatocytes. Aquat. Toxicol. 90: 322-332.

Caminada, D., Žaja, R., Smital, T., Fent, K. (2008). Human Pharmaceuticals Modulate Pgp1 (ABCB1) Transport Activity in the Fish Cell Line PLHC-1. Aquat. Toxicol. 90: 214-222.

Traven, L., Žaja, R., Lončar, J., Smital, T., Mićović, V. (2008). CYP1A induction potential and the concentration of priority pollutants in marine sediment samples – in vitro evaluation using the PLHC-1 fish hepatoma cell line. Toxicol. in vitro. 22: 1648-1656.

Žaja, R., Caminada, D., Lončar, J., Fent, K., Smital, T. (2008). Development and characterization of P-glycoprotein 1 (Pgp1; ABCB1) mediated doxorubicin resistant PLHC-1 epatoma fish cell line. Toxicol. Appl. Pharmacol. 227: 207-218.

Žaja, R., Munić, V., Smital, T. (2008). Cloning and mRNA expression analysis of an ABCG2 (BCRP) efflux transporter in rainbow trout (Oncorhynchus mykiss) liver and primary hepatocytes. Mar. Environ. Res. 66 (1): 77-79.

Epel, David; Stevenson, Charlotte N.; MacManus-Spencer, Laura A.; Luckenbach, Till; Hamdoun, Amro; Smital, Tvrtko.
 Efflux transporters: newly appreciated roles in protection against pollutants. //Environmental Science and Technology. 42 (2008) , 11; 3914-3920.

Tomić, Silvia; Dolanski Babić, Sanja; Ivek, Tomislav; Vuletić, Tomislav; Krča, Sanja; Livolant, Francoise; Podgornik, Rudi. Short-fragment Na-DNA dilute aqueous solutions: Fundamental length scales and screening. // Europhysics Letters. 81 (2008) , 6; 68003-p1-68003-p5 (članak, znanstveni).

3. Tomić, Silvia; Dolanski Babić, Sanja; Vuletić, Tomislav; Krča, Sanja; Ivanković, Dušica; Griparić, Lorena; Podgornik, Rudi. Dielectric relaxation of DNA aqueous solutions. //Physical Review E - Statistical Physics, Plasmas, Fluids, & Related Interdisciplinary Topics. 75 (2007) , 2 Part 1; 021905-1-021905-13 (članak, znanstveni).

Krča, S., Žaja, R., Čalić, V., Terzić, S., Grubešić, M., Ahel, M., Smital, T. (2007). Hepatic biomarker responses to organic contaminants in feral chub (Leuciscus cephalus) – laboratory characterisation and field study in the Sava river, Croatia. Environ. Tox. Chem. 26 (12): 2620-2633.

Žaja, R., Klobučar, R.S., Smital, T. (2007). Detection and functional characterization of Pgp1 (ABCB1) and MRP3 (ABCC3) efflux transporters in the PLHC-1 fish hepatoma cell line. Aquat. Toxicol. 81, 365-376.

Källqvist, Torsten; Milačič, Radmila; Smital, Tvrtko; Thomas, Kevin V; Vranes, Sanja; Tollefsen, Knut-Erik. Chronic toxicity of the Sava River (SE Europe) sediments and river water to the algae Pseudokirchneriella subcapitata. //Water Research. 42 (2007) , 8-9; 2146-2156.

Žaja, R., Klobučar, G.I.V., Klobučar R.S., Hackenberger B.K., Smital T. (2006). Haemolymph as compartment for efficient and non-destructive determination of P-glycoprotein (Pgp) mediated MXR activity in bivalves. Comp. Biochem. Phys. C. 143, 103-112.

Pivcevic, B., Žaja, R. (2006). Pesticides and their binary combinations as P-glycoprotein inhibitors in NIH 3T3/MDR1 cells. ETAP. 22, 268–276. 

Tomić, Silvia; Vuletić, Tomislav; Dolanski Babić, Sanja; Krča, Sanja; Ivanković, Dušica; Griparić, Lorena; Podgornik, Rudi. Screening and Fundamental Length Scales in Semidilute Na-DNA Aqueous Solutions. //Physical Review Letters. 97 (2006) ; 098303-1-098303-4.

2004 - 2000

Sauerborn, R., Polancec, D.S., Zaja, R., Smital, T. (2004). Identification of the multidrug resistance-associated protein (mrp) related gene in red mullet (Mullus barbatus). Mar. Environ. Res. 58, 199-204.

Smital, Tvrtko; Sauerborn, Roberta; Hackenberger, Branimir. Inducibility of the multixenobiotic resistance mechanism (MXR) transport activity in the marine mussel Mytilus galloprovincialis and the freshwater mussel Dreissena polymorpha. //Aquatic Toxicology. 65 (2003) ; 443-465.

Smital, Tvrtko; Sauerborn, Roberta. Measurement of the activity of multixenobiotic resistance mechanism in the common carp Cyprinus carpio. //Marine Environmental Research. 54 (2002) ; 449-453.

Krasko, Anatolij; Kurelec, Branko; Batel, Renato; Muller I.M.; Muller W.E.G. Potential multidrug resistance gene POHL : an ecologically relevant indicator in marine sponges. //Environmental toxicology and chemistry. 20 (2001) , 1; 198-204.

Kurelec, Branko; Smital, Tvrtko; Pivčević, Branka; Eufemia, Nancy; Epel, David. Multixenobiotic resistance, P-glycoprotein, and chemosensitizers. //Ecotoxicology. 9 (2000) , 5; 307-327.

Ramljak, Sanja; Hackenberger, Branimir; Smital, Tvrtko; Britvić, Smiljana.  Evaluation of the genotoxic and cytochrome P450 monooxigenase-inhibitory potential of Dicuran on procaryotic and eucaryotic test systems. //Journal of Environmental Science and Health - Part B: Pesticides, Food Contaminants, and Agricultural Wastes. 35 (2000) , 6; 751-770

Smital, Tvrtko; Sauerborn, Roberta; Pivčević, Branka; Krča, Sanja; Kurelec, Branko. Interspecies differences in P-glycoprotein mediated activity of multixenobiotic resistance mechanism in several marine and freshwater invertebrates. //Comparative Biochemistry and Physiology C. 126 (2000) ; 175-186.

1999 - 1995

Britvić, Smiljana; Kurelec, Branko. The effect of inhibitors of multixenobiotic resistance mechanism on the production of mutagens by Dreissena polymorpha in waters spiked with premutagens. //Aquatic toxicology. 47 (1999) , 2; 107-116.

Kurelec, Branko; Britvić, Smiljana; Pivčević, Branka; Smital, Tvrtko. Fragility of multixenobiotic resistance in aquatic organisms enhances the complexity of risk assessment. //Marine environmental research. 46 (1998) , 1-5; 415-419

Osmak, Maja; Brozović, Anamaria; Ambriović-Ristov, Andreja; Hadžija, Mirko; Pivčević, Branka; Smital, Tvrtko. Inhibition of apoptosis is the cause of resistance to doxorubicin in human breast adenocarcinoma cells. //Neoplasma. 45 (1998) , 4; 223-230.

Smital, Tvrtko; Kurelec, Branko. The activity of multixenobiotic resistance mechanism determined by rhodamine B-efflux method as a biomarker of exposure. //Marine environmental research. 46 (1998) , 1-5; 443-447.

Smital, Tvrtko; Kurelec, Branko. The chemosenzitizers of multixenobiotic resistance mechanism in aquatic invertebrates : a new class of pollutants. //Mutation research. 399 (1998) , 1; 43-53. 

Muleller, E.G. Werner; Riemer, Siegurd; Kurelec, Branko; Smodlaka, Nenad; Puškarić, Staša; Jagić, Bela; Mueller-Niklas, Gerald; Queric, V. Nadia. Chemosenzitizers of the multixenobiotic resistance in amorphous aggregates (marine snow) : etiology of mass killing on the benthos in the Northern Adriatic?. //Environmental toxicology and pharmacology. 6 (1998) , 4; 229-238.

Schroeder, C. Heinz; Badria, A. Farid; Ayyad, N. Seif; Batel, Renato; Wiens, Matthias; Hassanein, M.A. Hamdy; Kurelec, Branko; Mueller, E.G. Werner. Inhibitory effects of extracts from the marine alga Caulerpa taxifolia and of toxin from Caulerpa racemosa on multixenobiotic resistance in the marine sponge Geodia cydonium. //Environmental toxicology and pharmacology. 5 (1998) , 2; 119-126.

Smital, Tvrtko; Kurelec, Branko. The concentrations of inhibitors of multixenobiotic resistance mechanism in natural waters: The direct in vivo demonstration of their effect. //Environmental toxicology and chemistry. 16 (1997) , 10; 2164-2170.

Kurelec, Branko; Krča, Sanja; Lucić, Davor. Expression of multixenobiotic resistance mechanism in a marine mussel Mytilus galloprovincialisas as a biomarker of exposure to polluted environment. //Comparative biochemistry and physiology C : pharmacology, toxicology and endocrinology. 113 (1996) , 2; 283-289.

Kurelec, Branko; Waldmann, Petra; Zahn, Rudolf K. The modulation of protective effects of the multixenobiotic resistance mechanism in a clam Corbicula fluvinea. //Marine environmental research. 42 (1996) , 1-4; 383-387 .

 Mueller, Werner E.G.; Stefen, Renate; Rinkevich, Baruch; Matranga, Valeria; Kurelec, Branko. The multixenobiotic resistance mechanism in the marine sponge suberites domuncula - its potential applicability for the evaluation of environmental pollution by toxic compounds. //Marine biology. 125 (1996) , 1; 165-170.

Kurelec, Branko; Lucić, Dalibor; Pivčević, Branka; Krča, Sanja. Induction and reversion of multixenobiotic resistance in the marine snail Monodonta turbinata. //Marine Biology. 123 (1995) ; 305-312.

Kurelec, Branko; Pivčević, Branka; Müller, Werner E. G. Determination of pollutants with multixenobiotic -resistance inhibiting properties. //Marine Environmental Research. 39 (1995) ; 261-265.

Waldman, Petra; Pivčević, Branka; Müller, Werner E. G.; Zahn, Rudolf K.; Kurelec, Branko. Increased genotoxicity of acetylaminofluorene by modulators of multixenobiotic resistance mechanism: studies with the fresh water clam Corbicula fluminea. //Mutation Research - Genetic Toxicology. 342 (1995) ; 113-123.

Kurelec, Branko. Reversion of multixenobiotic resistance mechanism in gills of a marine mussel Mytilus galloprovincialis by model- and environmental-inhibitors of P170-glycoprotein. //Aquatic toxicology. 33 (1995) , 2; 93-103.

Müller, Werner E.G.; Koziol, Claudia; Kurelec, Branko; Dapper, Jutta; Batel, Renato; Rinkevich, Baruch. Combinatory effects of temperature stress and nonionic organic pollutants on stress protein (HSP70) gene expression in the freshwater sponge Ephydatia fluviatilis. //Environmental toxicology and chemistry. 14 (1995) , 7; 1203-1208.

1994 - ...

Kurelec, Branko; Krča, Sanja; Pivčević, Branka; Ugarković, Đurđica; Bachmann, Michael; Imsiecke, Georg; Müller, Werner E.G. Expression of P-glycoprotein gene in marine sponges. Identification and characterization of the 125 kDa drug-binding glycoprotein. //Carcinogenesis. 13 (1992) ; 69-76.

Kurelec, Branko; Pivčević, Branka. The multidrug resistance-like mechanism in the marine sponge Tethya aurantium. // Marine Environmental Research. 34 (1992) ; 249-253.

Kurelec, Branko; Pivčević, Branka. Evidence for a multixenobiotic resistance mechanism in the mussel Mytilus galloprovincialis. //Aquatic Toxicology. 19 (1991) ; 291-302.

Kurelec, Branko; Pivčević, Branka. Distinct glutathione-dependent enzyme activities and a verapamil-sensitive binding of xenobiotics in a fresh-water mussel Anodonta cygnea. //Biochemical and Biophysical Research Communications. 164 (1989) ; 934-940.

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LATEST ARTICLE

Multidrug and toxin extrusion (MATE) proteins are involved in the extrusion of endogenous compounds and xenobiotics across the plasma membrane. They are conserved from bacteria to mammals, with different numbers of genes within groups. Here, we present the frst data on identifcation and functional characterization of Mate proteins in zebrafsh (Danio rerio). Phylogenetic analysis revealed six Mates in teleost fsh, annotated as Mate3–8, which form a distinct cluster separated from the tetrapod MATEs/Mates. Synteny analysis showed that zebrafsh mate genes are orthologous to human MATEs. Gene expression analysis revealed that all the mate transcripts were constitutively and differentially expressed during embryonic development, followed by pronounced and tissue-specifc expression in adults. Functional analyses were performed using transport activity assays with model substrates after heterologous overexpression of fve zebrafsh Mates in HEK293T cells. The results showed that zebrafsh Mates interact with both physiological and xenobiotic substances but also substantially differ with respect to the interacting compounds and interaction strength in comparison to mammalian MATEs/Mates. Taken together, our data clearly indicate a potentially important role for zebrafsh Mate transporters in zebrafsh embryos and adults and provide a basis for detailed functional characterizations of single zebrafsh Mate transporters.

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