Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy
Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy
复制标题
DOI：
10.1016/s0887-8994(03)00407-7
复制
发表时间：
2004-02-01
影响因子：
3.8
通讯作者：
Taratuto, AL
中科院分区：
文献类型：
--
作者：
Lazarowski, A;Lubieniecki, F;Taratuto, AL
脑硬化症是一种常染色体显性遗传综合征，其特征是严重受累个体的药物难治性癫痫发作。结节性硬化症的耐药机制尚不清楚。蛋白质MDR-1（多药耐药）和MRP-1（多药耐药相关蛋白-1）与肿瘤细胞的化疗耐药性有关。然而，抗癫痫药物难治性与MDR-1或MRP-1脑表达之间的关系研究甚少。我们先前曾报告一例结节性硬化症合并难治性癫痫，其致癫痫性脑损伤的结节细胞表达多药耐药基因（MDR-1）。在这项回顾性研究中，我们描述了MDR-1和MRP-1的表达在致癫痫皮质结节的三个儿童结节性硬化症和难治性癫痫手术治疗。MDR-1和MRP-1蛋白的单克隆抗体用于免疫组织化学。在致癫痫皮质结节脑标本中，MDR-1和MRP-1蛋白在异常的气球细胞、发育不良的神经元、星形胶质细胞、小胶质细胞和一些血脑血管中呈强免疫反应性。观察到更广泛的MDR-1免疫反应。这些数据表明，结节性硬化症的难治性癫痫表型可能与致癫痫皮质结节中多药耐药MDR-1和MRP-1转运蛋白的表达有关。(C)2004年，Elsevier Inc. All rights reserved.
Tuberous sclerosis is an autosomal dominant syndrome characterized by seizures that are refractory to medication in severely affected individuals. The mechanism involved in drug resistance in tuberous sclerosis is unknown. The proteins MDR-1 (multidrug resistance) and MRP-1 (multidrug resistance-associated protein-1) are linked to chemotherapy resistance in tumor cells. However, the relationship between refractoriness to antiepileptic drugs and MDR-1 or MRP-1 brain expression has been poorly studied. We have previously described a case of tuberous sclerosis with refractory epilepsy that expressed multidrug resistance gene (MDR-1) in tuber cells from epileptogenic brain lesion. In this retrospective study, we describe the expression of MDR-1 and MRP-1 in the epileptogenic cortical tubers of three pediatric patients with tuberous sclerosis and refractory epilepsy surgically treated. Monoclonal antibodies for MDR-1 and MRP-1 proteins were used for immunohistochemistry. In epileptogenic cortical tuber brain specimens, MDR-1 and MRP-1 proteins were strongly immunoreactive in abnormal balloon cells, dysplastic neurons, astrocytes, microglial cells, and some blood-brain vessels. A more extensive MDR-1 immunoreactivity was observed. These data suggest that refractory epilepsy phenotype in tuberous sclerosis can be associated with the expression of both multidrug resistance MDR-1 and MRP-1 transporters in epileptogenic cortical tubers. (C) 2004 by Elsevier Inc. All rights reserved.