Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia
Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia
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DOI：
10.1016/j.seizure.2007.03.011
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发表时间：
2007-09-01
影响因子：
3
通讯作者：
Uzan, Mustafa
中科院分区：
文献类型：
--
作者：
Ak, Hatil;Ay, Bahadir;Uzan, Mustafa
近年来研究发现，在致痫组织中，耐药蛋白的过度表达可能与1/3的抗癫痫药物（AEDs）无效的癫痫患者有关。由于几种AED可以作为这些耐药蛋白的底物，因此这些蛋白的增强功能可以增加药物挤出，我们研究了28例局灶性皮质发育不良（FCD）患者手术切除的癫痫组织中多药耐药蛋白1（MDR 1）和多药耐药相关蛋白1（MRP 1）的表达，应用免疫与10例正常尸检脑组织比较，正常脑组织中神经元和星形胶质细胞未见MDR 1表达，少数脑组织中有MRP 1表达。MDR 1主要表达于血管内皮细胞。与正常脑相比，我们发现在绝大多数发育不良组织中，神经元和反应性星形胶质细胞中MDR 1和MRP 1表达强烈。大多数发育不良的神经元表现出中度至强烈的MRP 1免疫反应。在所研究的大多数标本中，内皮细胞同时显示MDR 1和MRP 1表达。这些结果与先前的研究一致，其中FCD患者的致癫痫脑组织中显示多药蛋白的过表达，难治性癫痫患者组织中药物转运蛋白的过表达可能解释了这些病理中耐药的一种可能机制。(c)2007年英国癫痫协会。由爱思唯尔有限公司出版。保留所有权利。
Recent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy.We studied expression of the muttidrug resistance protein 1 (MDR1) and muttidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dyspLasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues.Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied.Muttidrug transporters are over-expressed in the epiteptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epiteptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies. (c) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.