Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells.
Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells.
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DOI：
10.1186/1471-2202-11-41
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发表时间：
2010-03-25
期刊：
影响因子：
2.4
通讯作者：
Bubacco L
中科院分区：
文献类型：
--
作者：
Bisaglia M;Greggio E;Maric D;Miller DW;Cookson MR;Bubacco L
氧化应激被认为与帕金森病（PD）的发病机制有关。黑质多巴胺能神经元氧化应激的一个合理来源是氧化还原反应，该反应特别涉及多巴胺并产生各种有毒分子，即自由基和醌类。α-突触核蛋白，一种在路易体中发现的PD特征蛋白，也被认为参与PD的发病机制，α-突触核蛋白编码基因的点突变和扩增在家族型PD中被发现。我们利用稳定转染WT或A30P突变体α-synuclein的多巴胺能人神经母细胞瘤BE(2)-M17细胞系，研究α-synuclein对多巴胺毒性的影响。用乳酸脱氢酶法和荧光活化细胞分选法分析细胞毒性。无论是野生型还是突变型α-突触核蛋白的表达增加，都能增强细胞内多巴胺或多巴积累引起的细胞毒性。我们的研究结果表明，多巴胺和α-突触核蛋白之间的相互作用可导致神经元样背景下的细胞死亡。这里提供的数据与几种细胞毒性模型相容，包括α-突触核蛋白低聚物的形成和溶酶体降解的损害。
Oxidative stress has been proposed to be involved in the pathogenesis of Parkinson's disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species. α-Synuclein, a protein found in Lewy bodies characteristic of PD, is also thought to be involved in the pathogenesis of PD and point mutations and multiplications in the gene coding for α-synuclein have been found in familial forms of PD. We used dopaminergic human neuroblastoma BE(2)-M17 cell lines stably transfected with WT or A30P mutant α-synuclein to characterize the effect of α-synuclein on dopamine toxicity. Cellular toxicity was analyzed by lactate dehydrogenase assay and by fluorescence-activated cell sorter analysis. Increased expression of either wild-type or mutant α-synuclein enhances the cellular toxicity induced by the accumulation of intracellular dopamine or DOPA. Our results suggest that an interplay between dopamine and α-synuclein can cause cell death in a neuron-like background. The data presented here are compatible with several models of cytotoxicity, including the formation of α-synuclein oligomers and impairment of the lysosomal degradation.
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影响因子：
5.3
作者：
Mosharov, Eugene V.;Staal, Roland G. W.;Sulzer, David
通讯作者：
Sulzer, David
影响因子：
4.8
作者：
Lee, FJS;Liu, F;Niznik, HB
通讯作者：
Niznik, HB
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
4.8
作者：
Bisaglia, Marco;Mammi, Stefano;Bubacco, Luigi
通讯作者：
Bubacco, Luigi
影响因子：
2.4
作者：
HIRSCH, EC
通讯作者：
HIRSCH, EC