National Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Neurosci Res. 2009 Nov;65(3):236-44. doi: 10.1016/j.neures.2009.07.006. Epub 2009 Jul 22.
Neuron-restrictive silencer factor (NRSF)/neuronal repressor element-1 silencing transcription factor (REST) and its neuron-specific truncated form REST4 participates in the pathological processes of nervous system diseases, such as global ischemia, epilepsy, Huntington disease and so on. In this paper, we investigated the changes of NRSF and REST4 in a cellular model of Parkinson's disease (PD). Our results showed that neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP(+)) treatment triggered the mRNA and protein expression of NRSF and REST4, and caused both NRSF and REST4 proteins relocalized between the nucleus and cytoplasm in human dopaminergic SH-SY5Y cells. Redistribution of NRSF and REST4 derepressed the expression of target genes at late time points. Furthermore, alteration of NRSF and REST4 expression by overexpression or RNAi techniques elicited deleterious effects on cell viability of SH-SY5Y treated with toxic MPP(+).
神经元限制沉默因子 (NRSF)/神经元抑制元件-1 沉默转录因子 (REST)及其神经元特异性截断形式 REST4 参与神经系统疾病的病理过程，如全脑缺血、癫痫、亨廷顿病等。在本文中，我们研究了帕金森病 (PD)细胞模型中 NRSF 和 REST4 的变化。我们的结果表明，神经毒素 1-甲基-4-苯基-吡啶离子 (MPP(+)) 处理触发了 NRSF 和 REST4 的 mRNA 和蛋白质表达，并导致人多巴胺能 SH-SY5Y 细胞中的 NRSF 和 REST4 蛋白在核和细胞质之间重新分布。NRSF 和 REST4 的重分布使靶基因在晚期表达去抑制。此外，通过过表达或 RNAi 技术改变 NRSF 和 REST4 的表达对用有毒 MPP(+)处理的 SH-SY5Y 细胞活力产生了有害影响。
