The ATP-binding cassette transporters ABCB1 and ABCC1 are not regulated by hypoxia in immortalised human brain microvascular endothelial cells

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Background: ATP-binding cassette transporters at the blood-brain barrier are actively regulated upon ischemic stroke in a way that impedes the access of pharmacological compounds to the brain tissue. The luminal endothelial transporter ABCB1 was recently shown to be increased, whereas the abluminal transporter ABCC1 was decreased on ischemic brain capillaries. In vitro studies using epithelial cells suggested that ABCB1 is regulated during hypoxia in a hypoxia-inducible factor (HIF)-1a-dependent way. Methods: In order to investigate whether hypoxia might be responsible for the expression changes of ABCB1 and ABCC1 in the ischemic brain, the immortalised human brain microvascular endothelial cell line hCMEC/D3 was exposed to hypoxia (1%) or anoxia (0%). Cell lysates were analysed by Western blot to detect the protein expression of ABCB1, ABCC1, HIF-1a and HIF-2a. Results: During hypoxia, an accumulation of HIF-1a and HIF-2a was noticed in hCMEC/D3 cells that followed different time kinetics. Both HIF-1a and HIF-2a abundance increased within 4 h of hypoxia. HIF-1a levels decreased to below detection levels within 16 h of hypoxia, whereas HIF-2a remained elevated even after 48 h. No changes of ABCB1 and ABCC1 expression were detected, neither on the mRNA nor protein level. Conclusion: Our data suggests that other factors than hypoxia may be responsible for the expression changes of ATP-binding cassette transporters in the ischemic brain.
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Dokumententyp:
Wissenschaftliche Texte » Artikel, Aufsatz
Fakultät / Institut:
Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Neurologie
Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Anästhesiologie und Intensivmedizin
Medizinische Fakultät » Universitätsklinikum Essen » Institut für Physiologie
Dewey Dezimal-Klassifikation:
600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit » 610 Medizin und Gesundheit
Stichwörter:
Blood-brain barrier, hypoxia-inducible factor, multidrug resistance, stroke
Sprache:
Englisch
Kollektion / Status:
E-Publikationen / Dokument veröffentlicht
Dateien geändert am:
26.01.2012
Medientyp:
Text
Rechtliche Vermerke:
© 2011 Patak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Quelle:
In: Experimental & Translational Stroke Medicine 2011, 3:12