Dauchy, Sandrine; Miller, Florence; Couraud, Pierre-Olivier; Weaver, Richard, J.; Weksler, Babette; Romero, Ignacio A.; Scherrmann, Jean-Michel; De Waziers, Isabelle and Decleves, Xavier
(2009).
| DOI (Digital Object Identifier) Link: | https://doi.org/10.1016/j.bcp.2008.11.001 |
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| Google Scholar: | Look up in Google Scholar |
Abstract
We investigated the expression of genes encoding ABC transporters, cytochromes P450 (CYPs) and some transcription factors in the hCMEC/D3 immortalized human cerebral microvascular endothelial cell line, a promising <i>in vitro</i> model of the human BBB, and we compared these expressions to a non-brain endothelial cell line (HUVEC) and freshly human brain microvessels. qRT-PCR showed that the <i>MDR1, BCRP, MRP1, MRP3, MRP4</i> and <i>MRP5</i> genes were expressed and that the main CYP gene was <i>CYP2U1</i> in hCMEC/D3. The pattern of ABC and CYPs gene expression in hCMEC/D3 differed from HUVEC which did not express <i>MDR1,/i>. Moreover, expression of P-gp and BCRP was lower in hCMEC/D3 than in human brain microvessels but remain functional as shown by rhodamine 123 efflux assay. The gene encoding the aryl hydrocarbon receptor (AhR), a transcription factor that regulates the expression of some ABC and CYPs was highly expressed in hCMEC/D3 and HUVEC, while the pregnane-X-receptor (PXR) and the constitutive androstane receptor (CAR) were barely detected. We investigated the function of the AhR-mediated regulatory pathway in hCMEC/D3 by treating them with the AhR agonist TCDD. The expressions of two AhR-target genes, <i>CYP1A1</i> and <i>CYP1B1</i>, were increased 26-fold and 28-fold. But the expressions of ABC transporter genes were not significantly altered. We have thus determined the pattern of expression of the genes encoding ABC transporters, CYPs and three transcription factors in hCMEC/D3 and shown that the AhR pathway might afford an original functional transport and metabolic pattern in cerebral endothelial cells that is different from other peripheral endothelial cells.
| Item Type: | Article |
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| Copyright Holders: | 2008 Elsevier Inc. |
| ISSN: | 1873-2968 |
| Keywords: | hCMEC/D3 cell line; ABC transporters; CYP; AhR; blood–brain barrier |
| Academic Unit/School: | Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences Faculty of Science, Technology, Engineering and Mathematics (STEM) |
| Interdisciplinary Research Centre: | Biomedical Research Network (BRN) |
| Item ID: | 12630 |
| Depositing User: | Astrid Peterkin |
| Date Deposited: | 12 Dec 2008 08:10 |
| Last Modified: | 17 Nov 2016 14:55 |
| URI: | http://oro.open.ac.uk/id/eprint/12630 |
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