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Expression and functional characterization of ABCG2 in brain endothelial cells and vessels
Abstract
Delivery of drugs to the brain is impeded by the activity of efflux pumps expressed by endothelial cells of brain vasculature. The ATP binding cassette (ABC) transporters, among which ABCB1/MDR1 P‐glycoprotein and ABCC1/multidrug resistance‐associated protein 1 are expressed in brain endothelial cells, participate in drug efflux properties of the blood‐brain barrier (BBB). Searches of the EST (expressed sequence tags) database with the conserved ABC domain, conducted to identify other ABC transporters expressed in the BBB, recovered 15 ABC transporter sequences expressed in human brain cDNA libraries. One of these sequences, identical to ABCG2 , was highly expressed in cultured human cerebromicrovascular endothelial cells and human brain tissue at both mRNA and protein levels. Overexpression of human ABCG2 in immortalized rat brain endothelial cells resulted in enhanced polarized abluminal to luminal transport of various substrates tested in the in vitro BBB model. Brain vessels extracted from tissue sections of nonmalignant human brain and glioblastoma tomors by laser capture microdissection microscopy and analyzed by real‐time polymerase chain reaction showed higher expression of ABCG2 relative to ABCB1/MDR1 and ABCC1/MRP1. ABCG2 was up‐regulated in both glioblastoma vessels and parenchymal tissue. These studies suggest a role for brain endothelial ABCG2 transporter in modulating drug delivery to the brain and in conferring drug resistance to glioblastomas.
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Cited by
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Helms, H. C., Abbott, N. J., Burek, M., Cecchelli, R., Couraud, P.-O., Deli, M. A., Förster, C., Galla, H. J., Romero, I. A., Shusta, E. V., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16630991 · Cited by 843
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Mao, Q. (2005) · The AAPS Journal · doi:10.1208/aapsj070112 · Cited by 405
Perrière, N., Demeuse, P., Garcia, E., Regina, A., Debray, M., Andreux, J. ‐., Couvreur, P., Scherrmann, J. ‐., Temsamani, J., Couraud, P. ‐., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.03020.x · Cited by 330
Cisternino, S., Mercier, C., Bourasset, F., Roux, F., & Scherrmann, J.-M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2033 · Cited by 329
Metadata
- Authors
- Zhang, W., Mojsilovic-Petrovic, J., Andrade, M. F., Zhang, H., Ball, M., & Stanimirovic, D. B.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-09
- Volume
- 17
- Issue
- 14
- Pages
- 1-24
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2164604975
- Cited by
- 204
- References
- 0
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- closed
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- Zhang, W., Mojsilovic-Petrovic, J., Andrade, M. F., Zhang, H., Ball, M., & Stanimirovic, D. B. (2003). Expression and functional characterization of ABCG2 in brain endothelial cells and vessels. The FASEB Journal. https://doi.org/10.1096/fj.02-1131fje
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