Membrane transporters – first line of defense against xenobiotics

Popović, Marta; Žaja, Roko; Lončar, Jovica; Smital, Tvrtko Membrane transporters – first line of defense against xenobiotics. In: Znanstveni susreti 3. vrste (7 July 2011 - 8 July 2011) Zagreb, Hrvatska. (Unpublished)

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Abstract

Uptake and efflux membrane transporters are often rate limiting step in detoxification of foreign compounds, including environmental contaminants and drugs. Mainly due to the biomedical research, uptake transporters of families SLC21 and SLC22, as well as efflux transporters of ABC superfamily are known to play crucial role in delivery and disposition of toxins and drugs in mammals. However, the role of these transporters in toxicological response of aquatic organisms has not been addressed in detail. Therefore, the aim of our research is to fill this knowledge gap and determine function and importance of uptake and efflux transporters in fish using zebrafish (Danio rerio) as a model organism. Methods used include: gene sequences retrieval from available databases, phylogenetic analysis, expression analysis, protein overexpression in heterologous expression systems and functional assays (ATPase assay and uptake assay using radioactively labeled substrates). Among our major recent achievements is the functional characterization of dominant transporters in zebrafish liver: uptake transporter Oatp1d1 (Slc211d1) and ABC transporter Pgp (Abcb1). We showed that Oatp1d1 is a functional ortholog of human OATP1A2, 1B1 and 1B3, having an essential physiological role in hormone transport. Furthermore, it is potentially a rate limiting step for the elimination of high priority environmental pollutants. We characterized fish Pgp (Abcb1) as one of the major transporters involved in elimination of hydrophobic pollutants in hepatocytes. We demonstrated that both, uptake and efflux transporters have to be taken together in understanding disposition and toxicity of environmental contaminants in aquatic organisms, a concept only recently recognized in ecotoxicology.

Item Type:	Unpublished conference/workshop items or lecture materials
Uncontrolled Keywords:	membrane transporters; SLC21; SLC22; environmental contaminants
Subjects:	NATURAL SCIENCES > Interdisciplinary Natural Sciences > Marine Science NATURAL SCIENCES > Interdisciplinary Natural Sciences > Environmental Science
Divisions:	Division for Marine and Enviromental Research
Depositing User:	Marta Popović
Date Deposited:	24 Sep 2012 13:22
URI:	http://fulir.irb.hr/id/eprint/355

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