engleski

Interaction of environmental contaminants with zebrafish uptake transporter Oatp1d1 (Slco1d1)

Membrane transporters are key determinants of toxicological response to xenobiotics. Polyspecific transporters from the OATP/Oatp superfamily mediate uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol and is predominantly expressed in liver, brain and testes. In this study we have characterized zebrafish Oatp1d1 transporter in relation to the transport of foreign compounds. We have developed a novel assay for testing Oatp1d1 interactors, using the fluorescent probe Lucifer yellow (LY). At the environmentally relevant concentrations, perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil, diclofenac, 17α-ethynilestradiol (EE2) and caffeine act as high affinity Oatp1d1 substrates, whereas perfluorooctanoic acid (PFOA) and synthetic estrogens 17β – estradiol (E2) and estrone (E1) can modulate Oatp1d1 activity as potent inhibitors. Considering the tissue localization of Oatp1d1, its inhibition could be implicated in (1) inhibition of Oatp1d1-mediated uptake of excess steroid hormone conjugates into hepatocytes, and (2) inhibition of dehydroepiandrosterone sulphate (DHEAS) uptake into the brain and testes. The study offers new insights in the understanding of uptake processes of environmental contaminants and contributes to the characterization of zebrafish as a model species. Characterization of Oatp1d1 in relation to xenobiotic transport could foster better understanding of the mode(s) of action of tested compounds, and enable more reliable predictions of their disposition and possible harmful effects in fish.

uptake transporter; Oatp1d1; zebrafish; environmental pollutants

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