Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain
| Autor: | Johannes C. Baayen, Rik J. Scheper, Paul van der Valk, Sieger Leenstra, S. Redeker, Marja Ramkema, Jan A. Gorter, Wim G.M. Spliet, Eleonora Aronica, Dirk Troost, George L. Scheffer, Erwin A. van Vliet |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Pathology, Other departments, Neurosurgery, Rehabilitation Medicine, Cellular and Computational Neuroscience (SILS, FNWI), Faculteit der Geneeskunde |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Abcg2 Blotting Western Oligodendroglioma Astrocytoma Biology Hippocampus Western blot SDG 3 - Good Health and Well-being Glioma medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Tissue Distribution Microvessel Cerebral Cortex Sclerosis medicine.diagnostic_test Brain Neoplasms Microcirculation Brain Human brain Cortical dysplasia medicine.disease Immunohistochemistry Multidrug Resistance-Associated Protein 2 Neoplasm Proteins medicine.anatomical_structure Neurology biology.protein ATP-Binding Cassette Transporters Endothelium Vascular Epilepsies Partial Neurology (clinical) Multidrug Resistance-Associated Proteins |
| Zdroj: | Epilepsia, 46(6), 849-857. Wiley-Blackwell Epilepsia, 46(6), 849-857. Wiley-Blackwell Publishing Ltd |
| ISSN: | 0013-9580 |
| DOI: | 10.1111/j.1528-1167.2005.66604.x |
| Popis: | Purpose: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)-related proteins. Recently, upregulation of different MDR proteins has been shown in human epilepsy-associated conditions. This study investigated the expression and cellular distribution of BCRP in human control and epileptic brain, including a large number of both neoplastic and nonneoplastic specimens from patients with chronic pharmacoresistant epilepsy. Methods: Several epileptogenic pathologies, such as hippocampal sclerosis (HS), focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumor, oligodendroglioma astrocytoma, and glioblastoma multiforme were studied by using Western blot and immunocytochemistry. Results: With Western blot, we could demonstrate the presence of BCRP in both normal and epileptic human brain tissue. In contrast to P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) 2, BCRP expression levels did not change in tissue from patients with HS, compared with control hippocampus. No BCRP immunoreactivity was observed in glial or neuronal cells, including reactive astrocytes and dysplastic neurons in FCD. BCRP expression was, however, increased in tumor brain tissue. Immunocytochemistry demonstrated that BCRP was exclusively located in blood vessels and was highly expressed at the luminal cell surface and in newly formed tumor capillaries. This localization closely resembles that of P-gp. The higher expression observed in astrocytomas by Western blot analysis was related to the higher vascular density within the tumor tissue. Conclusions: These results indicate a constitutive expression of BCRP in human endothelial cells, representing an important barrier against drug access to the brain. In particular, the strong BCRP expression in the microvasculature of epileptogenic brain tumors could critically influence the bioavailability of drugs within the tumor and contribute to pharmacoresistance. |
| Databáze: | OpenAIRE |
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