Overexpression of Human MRP1 in Neurons causes resistance to Antiepileptic Drugs in Drosophila Seizure Mutants
文献类型：期刊论文
| 作者 | Huang, Fu-De
|
| 刊名 | JOURNAL OF NEUROGENETICS
 |
| 出版日期 | 2011 |
| 卷号 | 25期号:4页码:201-206 |
| 关键词 | refractory epilepsy (RE) bang senseless (bss) transporter voltage-gated sodium channel (VGSC) pore sodium phenytoin (PHT) valproic acid (VPA) MEDICALLY INTRACTABLE EPILEPSY BANG-SENSITIVE MUTANTS TRANSPORTERS SUPPRESSION PROTEINS CHANNELS BEHAVIOR |
| ISSN号 | 0167-7063 |
| 通讯作者 | Huang, FD (reprint author), 320 Yue Yang Rd,SIBS 163, Shanghai 200031, Peoples R China,zhenguoliu2004@yahoo.com.cn ; fdhuang@ion.ac.cn |
| 英文摘要 | Multidrug resistance-associated protein 1 (MRP1), an efflux multidrug transporter, was shown to be elevated in both glia and neurons in seizure focus in refractory epilepsy patients. Up-regulation of MRP1 and other multidrug transporters in perivascular astrocytes was suggested to cause resistance to antiepileptic drugs (AEDs) by reducing the concentration of AEDs at the epileptogenic areas. However, it is not known whether the up-regulation of MRP1 in neurons can cause resistance to AEDs, such as sodium phenytoin (PHT) and valproic acid (VPA). PHT inhibits voltage-gated sodium channel (VGSC) by occluding it, but whether PHT enters the channel through its inner or outer pore is not known. The authors overexpressed human MRP1 protein only in neurons in a Drosophila genetic seizure model, bang senseless (bss) mutants. The authors found that overexpression of MRP1 blocked the attenuation of the seizure behavior of bss mutants by acute and chronic application of PHT, and by chronic application of VPA. Conversely, overexpression of MRP1 in neurons increased the tolerance of bss flies to high-dosage PHT and VPA. Thus, up-regulation of MRP1 expression only in neurons causes resistance to AED in seizure flies. Moreover, the current data suggest that PHT enters VGSC through its inner pore. |
| 学科主题 | Genetics & Heredity ; Neurosciences & Neurology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China[81071026]; 973 program[2011CBA00408, 81071025] |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1522]  |
| 专题 | 上海神经科学研究所_神经所(总) 上海神经科学研究所_神经退行性疾病研究小组 |
| 推荐引用方式 GB/T 7714 | Huang, Fu-De. Overexpression of Human MRP1 in Neurons causes resistance to Antiepileptic Drugs in Drosophila Seizure Mutants[J]. JOURNAL OF NEUROGENETICS,2011,25(4):201-206. |
| APA | Huang, Fu-De.(2011).Overexpression of Human MRP1 in Neurons causes resistance to Antiepileptic Drugs in Drosophila Seizure Mutants.JOURNAL OF NEUROGENETICS,25(4),201-206. |
| MLA | Huang, Fu-De."Overexpression of Human MRP1 in Neurons causes resistance to Antiepileptic Drugs in Drosophila Seizure Mutants".JOURNAL OF NEUROGENETICS 25.4(2011):201-206. |
入库方式： OAI收割
来源：上海神经科学研究所
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