Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells
Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells
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DOI：
10.1016/j.biocel.2009.05.008
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Ghafourifar, Pedram
中科院分区：
文献类型：
--
作者：
Parihar, Mordhwaj S.;Parihar, Arti;Ghafourifar, Pedram
α -突触核蛋白的过度表达和氧化应激与帕金森病的神经元细胞死亡有关。α -突触核蛋白与线粒体相关，α -突触核蛋白的过度积累导致线粒体功能受损。然而，α -突触核蛋白引起线粒体损伤的机制尚不完全清楚。我们最近报道了α -突触核蛋白与线粒体相关，α -突触核蛋白的过度表达导致线粒体蛋白的硝化作用和线粒体细胞色素c的释放。[j]李建平，李建平，李建平，等。线粒体α -突触核蛋白对氧化应激的影响。中国生物医学工程学报，2009;25(3):444 - 444。本研究表明，α -突触核蛋白A53T或A30P突变体或野生型在人神经母细胞瘤细胞中的过表达增强了α -突触核蛋白的聚集。免疫印迹和免疫金电子透射显微镜显示，α -突触核蛋白聚集体定位在过表达细胞的线粒体内。过表达的细胞表现为线粒体活性氧增加，蛋白酪氨酸硝化增加，线粒体跨膜电位降低，细胞呼吸受到阻碍。这些发现表明线粒体在细胞对α -突触核蛋白的反应中起重要作用。2009爱思唯尔有限公司版权所有。
Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood. We recently reported that alpha-synuclein associates with mitochondria and that overexpression of alpha-synuclein causes nitration of mitochondrial proteins and release of cytochrome c from the mitochondria. [Parihar M.S., Parihar A., Fujita M., Hashimoto M., Ghafourifar P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci. 2008a;65:1272-1284]. The present study shows that overexpression of alpha-synuclein A53T or A30P mutants or wild-type in human neuroblastoma cells augmented aggregation of alpha-synuclein. Immunoblotting and immuno-gold electron transmission microscopy show localization of alpha-synuclein aggregates within the mitochondria of overexpressing cells. Overexpressing cells show increased mitochondrial reactive oxygen species, increased protein tyrosine nitration, decreased mitochondrial transmembrane potential, and hampered cellular respiration. These findings suggest an important role for mitochondria in cellular responses to alpha-synuclein. (C) 2009 Elsevier Ltd. All rights reserved.