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The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro : a comparison of primary human hepatocytes and OATP-transfected HEK293 cells

The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro : a comparison of primary human hepatocytes and OATP-transfected HEK293 cells

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FISCHER, Andreas, Stefan J. HÖGER, Kerstin STEMMER, Daniel FEURSTEIN, Daniel KNOBELOCH, A. NUSSLER, Daniel DIETRICH, 2010. The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro : a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. In: Toxicology and Applied Pharmacology. 245(1), pp. 9-20. ISSN 0041-008X. eISSN 1096-0333

@article{Fischer2010organ-7550, title={The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro : a comparison of primary human hepatocytes and OATP-transfected HEK293 cells}, year={2010}, doi={10.1016/j.taap.2010.02.006}, number={1}, volume={245}, issn={0041-008X}, journal={Toxicology and Applied Pharmacology}, pages={9--20}, author={Fischer, Andreas and Höger, Stefan J. and Stemmer, Kerstin and Feurstein, Daniel and Knobeloch, Daniel and Nussler, A. and Dietrich, Daniel} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/7550"> <dc:creator>Dietrich, Daniel</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7550"/> <dc:contributor>Höger, Stefan J.</dc:contributor> <dc:language>eng</dc:language> <dc:creator>Höger, Stefan J.</dc:creator> <dc:contributor>Knobeloch, Daniel</dc:contributor> <dc:contributor>Feurstein, Daniel</dc:contributor> <dc:format>application/pdf</dc:format> <dcterms:issued>2010</dcterms:issued> <dc:creator>Nussler, A.</dc:creator> <dc:contributor>Nussler, A.</dc:contributor> <dc:creator>Feurstein, Daniel</dc:creator> <dc:contributor>Stemmer, Kerstin</dc:contributor> <dcterms:bibliographicCitation>First publ. in: Toxicology and Applied Pharmacology 245 (2010), 1, pp. 9-20</dcterms:bibliographicCitation> <dc:creator>Knobeloch, Daniel</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:35:20Z</dc:date> <dcterms:title>The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro : a comparison of primary human hepatocytes and OATP-transfected HEK293 cells</dcterms:title> <dcterms:abstract xml:lang="eng">Cellular uptake of microcystins (MCs), a family of cyclic cyanobacterial heptapeptide toxins, occurs via specific organic anion transporting polypeptides (OATPs), where MCs inhibit serine/threonine-specific protein phosphatase (PP). Despite comparable PP-inhibitory capacity, MCs differ greatly in their acute toxicity, thus raising the question whether this discrepancy results from MC-specific toxikokinetic rather than toxicodynamic differences. OATP-mediated uptake of MC congeners MCLR, -RR, -LW and LF was compared in primary human hepatocytes and HEK293 cells stably expressing recombinant human OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3 in the presence/absence of OATP substrates taurocholate (TC) and bromosulfophthalein (BSP) and measuring PP-inhibition and cytotoxicity. Control vector expressing HEK293 were resistant to MC cytotoxicity, while TC and BSP competition experiments reduced MC cytotoxicity in HEK293-OATP transfectants, thus confirming the requirement of OATPs for trans-membrane transport. Despite comparable PP-inhibiting capabilities, MCLW and -LF elicited cytotoxic effects at lower equimolar concentrations than MCLR and MCRR, hence suggesting congener selective transport into HEK293-OATP transfectants and primary human hepatocytes. Primary human hepatocytes appeared one order of magnitude more sensitive to MC congeners than the corresponding HEK293 -OATP transfectants. Although the latter maybe due to a much lower level of PPs in primary human hepatocytes, the presence of OATPs other than 1B1 or 1B3 may have added to an increased uptake of MCs. In view of the high sensitivity of human hepatocytes and currently MCLR-only based risk calculations, the actual risk of human MC-intoxication and ensuing liver damage could be underestimated in freshwater cyanobacterial blooms where MCLW and-LF predominate.</dcterms:abstract> <dc:contributor>Dietrich, Daniel</dc:contributor> <dc:rights>deposit-license</dc:rights> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-05-31T22:25:04Z</dcterms:available> <dc:creator>Stemmer, Kerstin</dc:creator> <dc:contributor>Fischer, Andreas</dc:contributor> <dc:creator>Fischer, Andreas</dc:creator> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> </rdf:Description> </rdf:RDF>

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