RNA interference targeting α-synuclein attenuates methamphetamine-induced neurotoxicity in SH-SY5Y cells
RNA interference targeting α-synuclein attenuates methamphetamine-induced neurotoxicity in SH-SY5Y cells
复制标题
针对 α-突触核蛋白的 RNA 干扰可减轻 SH-SY5Y 细胞中甲基苯丙胺诱导的神经毒性
DOI：
10.1016/j.brainres.2013.05.016
复制
发表时间：
2013-07-12
期刊：
影响因子：
2.9
通讯作者：
Liu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Ling;Huang, Enping;Liu, Chao
α-突触核蛋白（α-syn）在神经元中含量丰富，据称在帕金森病的病理生理学中发挥着关键作用。 α-syn 的过度表达已被证明在甲基苯丙胺 (METH) 诱导的体内和体外模型中具有毒性，该模型具有帕金森病样病理学。然而，α-syn 介导的 METH 诱导的神经元毒性的确切机制仍然未知。在本研究中，人多巴胺能样神经母细胞瘤SH-SY5Y细胞被用作METH诱导的体外模型。与α-syn野生型细胞相比，在沉默α-syn表达并随后进行METH处理后，发现细胞活力显着增加，并且通过在该模型中敲低α-syn表达，减轻了METH处理后对细胞的形态损伤。 METH处理后，酪氨酸羟化酶（TH）、多巴胺转运蛋白（DAT）和囊泡单胺转运蛋白2（VMAT-2）的表达水平显着降低，活性氧（ROS）、一氧化氮合酶（NOS）和氮（NO）的活性/水平显着升高。然而，这些表达水平的变化在用α-syn-shRNA转染的细胞中发生逆转。这些结果表明TH、DAT、VMAT-2、ROS和NOS可能参与α-syn介导的METH诱导的神经元毒性。 (C) 2013 Elsevier B.V. 保留所有权利。
The protein alpha-synuclein (alpha-syn) is abundant in neurons and has been claimed to play critical roles in the pathophysiology of Parkinson's disease. Overexpression of alpha-syn has been shown to be toxicity in methamphetamine (METH)-induced model in vivo and in vitro which has Parkinson's-like pathology. However, the exact mechanisms underlying toxicity of alpha-syn mediated METH-induced neuron remain unknown. In the present study, human dopaminergic-like neuroblastoma SH-SY5Y cells were used as METH-induced model in vitro. Cell viability was found to be dramatically increased after silencing alpha-syn expression followed by METH treatment compared with a-syn wild-type cells and the morphological damage to cells after METH treatment was abated through knockdown of alpha-syn expression in this model. The expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2(VMAT-2) were significantly decreased and the activity/levels of reactive oxygen species (ROS), nitric oxide synthase (NOS) and nitrogen (NO) were notably increased after METH treatment. However, the changes of these expression levels were reversed in cells transfected with alpha-syn-shRNA. These results suggested that TH, DAT, VMAT-2, ROS and NOS maybe involved in alpha-syn mediated METH-induced neuronal toxicity. (C) 2013 Elsevier B.V. All rights reserved.