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首页> 外文期刊>The international journal of biochemistry and cell biology >Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.
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Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.

机译:α-突触核蛋白的过表达和聚集通过增加人类神经母细胞瘤细胞中的氧化应激而加剧线粒体功能受损。

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摘要

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.
机译:帕金森氏病的神经元细胞死亡与α-突触核蛋白的过表达和氧化应激有关。 α-突触核蛋白与线粒体缔合,α-突触核蛋白的过度积累导致线粒体功能受损。但是,由α-突触核蛋白引起的线粒体损伤的机制尚不完全清楚。我们最近报道,α-突触核蛋白与线粒体缔合,α-突触核蛋白的过度表达导致线粒体蛋白硝化并从线粒体释放细胞色素c [Parihar MS,Parihar A.,Fujita M.,桥本M.,Ghafourifar P.线粒体α-突触核蛋白的缔合引起氧化应激。细胞分子生命科学2008a; 65:1272-1284]。本研究表明,人类神经母细胞瘤细胞中α-突触核蛋白A53T或A30P突变体或​​野生型的过表达增强了α-突触核蛋白的聚集。免疫印迹和免疫金电子透射显微镜检查显示,α-突触核蛋白聚集体位于过表达细胞线粒体内。过表达的细胞显示线粒体活性氧增加,蛋白质酪氨酸硝化增加,线粒体跨膜电位降低以及细胞呼吸受阻。这些发现表明线粒体在细胞对α-突触核蛋白的反应中具有重要作用。

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