PMID: identifiant
de la référence Pubmed : |
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 (22553972)  |
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| titre : |
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ATP-binding cassette transporters in immortalised human brain microvascular endothelial cells in normal and hypoxic conditions |
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| auteur(s) : |
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Christian Lindner1, 2, Alexander Sigrüner3, Franziska Walther1, Ulrich Bogdahn1, Pierre Couraud4, Gert Schmitz1, Felix Schlachetzki ( ) 1 |
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| résumé : |
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Background
Rapid reperfusion following ischemia is the most effective therapy in stroke therapy. However, the success may be compromised by ischemia & reperfusion (I/R) injury and at the human blood-brain barrier (BBB), therefore the effects on transendothelial transport are of special interest. Current studies suggest the ATP-binding cassette (ABC) transporters to be regulated upon ischemic stroke in a way that impedes the effects of drug therapy. The immortalised human brain microvascular endothelial cell line hCMEC/D3 provides most of the unique properties of the BBB with respect to transport and might be a reliable in vitro model to study transendothelial transport after I/R.
Methods
We exposed hCMEC/D3 cells to 24 hours of hypoxia alone and to hypoxia followed by 60 min of reoxygenisation as an in vitro model for I/R. Western blot showed mild upregulation of hypoxia inducible factor (HIF-1α) after hypoxia alone and RNA lysates were analysed with a well-established real-time RT-PCR-based TaqMan low-density array detecting 47 of 48 known human ABC transporters.
Results
No significant increases of ABC mRNA expression levels were detected neither in hypoxic nor in I/R samples. However, slight decrease of ABCC1 in hypoxic and I/R samples and of ABCA10 and ABCD3 in I/R samples was observed.
Conclusion
Our data suggests that hCMEC/D3 cell line and - at the moment - in vitro models in general are a poor basis for stroke research but may be enhanced by co-culturing more cells of the neurovascular unit inducing an overall ischemic response at the BBB. |
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| domaine : |
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langue du texte
intégral : |
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Anglais |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1186/2040-7378-4-9 |
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| journal : |
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Experimental & Translational Stroke Medicine |
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| Audience : |
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internationale |
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| date de publication : |
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2012 |
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| volume : |
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4 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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9 |
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| mots-clés auteur : |
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Blood-brain barrier – Ischemia/reperfusion injury – Hypoxia-inducible factor – Multidrug resistance – ABC transporters – Stroke |
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| Projet Européen : |
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| Acronyme |
European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 202272, IP |
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