Kubota, H and Ishihara, H and Langmann, Thomas and Schmitz, Gerd and Stieger, B and Wieser, HG and Yonekawa, Y and Frei, Karl (2006) Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis. EPILEPSY RESEARCH, 68 (3). pp. 213-228. ISSN 0920-1211, 1872-6844
Full text not available from this repository. (Request a copy)Abstract
Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 (ABCC1) and 2 (ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascularendothelial cells (HBMEC) from epileptic patients (HBMEC-EP1) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue. the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that MDR1, MRP1 as well as MRP5 (ABCC5) and MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood-brain barrier (BBB). (c) 2005 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TEMPORAL-LOBE EPILEPSY; MEDICALLY INTRACTABLE EPILEPSY; RAT-BRAIN; REFRACTORY EPILEPSY; DRUG TRANSPORTERS; MESSENGER-RNA; HUMAN TISSUES; IN-VITRO; EXPRESSION; BARRIER; blood-brain barrier; drug resistance; epilepsy; hippocampal sclerosis; multidrug resistance-associated proteins; P-glycoprotein |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Feb 2021 10:21 |
| Last Modified: | 18 Feb 2021 10:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34835 |
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