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<title lang=en>Polarized location of SLC and ABC drug transporters in monolayer-cultured human hepatocytes.</title>
<creator>Le Vee, Marc</creator>
<creator>Jouan, Elodie</creator>
<creator>Noel, Gregory</creator>
<creator>Stieger, Bruno</creator>
<creator>FARDEL, Olivier</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Division of Clinical Pharmacology and Toxicology ; University hospital of Zurich [Zurich]</contributor>
<description>International audience</description>
<source>ISSN: 0887-2333</source>
<source>Toxicology in Vitro</source>
<publisher>Elsevier</publisher>
<identifier>hal-01141725</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/file/Polarized%20location%20of%20SLC.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725</source>
<source>Toxicology in Vitro, Elsevier, 2015, 29 (5), pp.938-946. 〈10.1016/j.tiv.2015.03.019〉</source>
<identifier>DOI : 10.1016/j.tiv.2015.03.019</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tiv.2015.03.019</relation>
<identifier>PUBMED : 25862123</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/25862123</relation>
<language>en</language>
<subject lang=en>Canalicular secretion</subject>
<subject lang=en>Primary culture</subject>
<subject lang=en>Polarization</subject>
<subject lang=en>Drug transporter</subject>
<subject lang=en>Hepatocytes</subject>
<subject>[SDV] Life Sciences [q-bio]</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Human hepatocytes cultured in a monolayer configuration represent a well-established in vitro model in liver toxicology, notably used in drug transporter studies. Polarized status of drug transporters, i.e., their coordinated location at sinusoidal or canalicular membranes, remains however incompletely documented in these cultured hepatocytes. The present study was therefore designed to analyze transporter expression and location in such cells. Most of drug transporters were first shown to be present at notable mRNA levels in monolayer-cultured human hepatocytes. Cultured human hepatocytes, which morphologically exhibited bile canaliculi-like structures, were next demonstrated, through immunofluorescence staining, to express the influx transporters organic anion transporting polypeptide (OATP) 1B1, OATP2B1 and organic cation transporter (OCT) 1 and the efflux transporter multidrug resistance-associated protein (MRP) 3 at their sinusoidal pole. In addition, the efflux transporters P-glycoprotein and MRP2 were detected at the canalicular pole of monolayer-cultured human hepatocytes. Moreover, canalicular secretion of reference substrates for the efflux transporters bile salt export pump, MRP2 and P-glycoprotein as well as sinusoidal drug transporter activities were observed. This polarized and functional expression of drug transporters in monolayer-cultured human hepatocytes highlights the interest of using this human in vitro cell model in xenobiotic transport studies.</description>
<date>2015-04-07</date>
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