Overexpression of F(0)F(1)-ATP synthase alpha suppresses mutant huntingtin aggregation and toxicity in vitro.
Overexpression of F(0)F(1)-ATP synthase alpha suppresses mutant huntingtin aggregation and toxicity in vitro.
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F(0)F(1)-ATP 合酶 α 的过度表达可抑制突变型亨廷顿蛋白聚集和体外毒性。
DOI：
10.1016/j.bbrc.2009.10.139
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发表时间：
2009
影响因子：
3.1
通讯作者：
Cuiqing Zhu
中科院分区：
文献类型：
--
作者：
Hong;Yuxia Xu;Xiao;Hong Zhao;Jie Yan;Xiao;Jing;Cuiqing Zhu
亨廷顿氏病（HD）和其它多聚谷氨酰胺（polyQ）神经变性疾病的特征在于疾病蛋白的神经元积累，表明细胞处理异常蛋白的能力受到损害。F0 F1-ATP合成酶α是一种多亚基蛋白，位于真核细胞线粒体内，属于应激蛋白HSP 60家族。目前，越来越多的证据表明F0 F1-ATP合成酶α可能在阿尔茨海默病（Alzheimer's disease，AD）和帕金森病（Parkinson's disease，PD）等神经退行性疾病中发挥作用。近年来研究发现ATP合成酶α通过降低ROS的产生对铁负荷大鼠原代心肌细胞具有保护和治疗作用。然而，关于ATP合酶α在细胞死亡和神经变性中的作用知之甚少。在这里，我们证明了ATP合成酶α的过表达抑制了转染的SH-SY 5 Y细胞系中亨廷顿蛋白（htt）polyQ的聚集和毒性。ATP合成酶α的过表达能够保护由多聚谷氨酰胺扩增的htt引起的细胞死亡。在转染的SH-SY 5 Y细胞中，通过polyQ聚集、Western印迹分析和过滤陷阱分析（FTA）估计ATP合酶α的瞬时过表达抑制聚集体形成。结果表明，ATP合成酶α在体外对多聚谷氨酰胺聚集体的形成和毒性有较强的抑制作用，提示ATP合成酶α具有新的神经保护作用。
Huntington’s disease (HD) and other polyglutamine (polyQ) neurodegenerative diseases are characterized by neuronal accumulation of the disease protein, suggesting that the cellular ability to handle abnormal proteins is compromised. As a multi-subunit protein localized in the mitochondria of eukaryotic cells, the F0F1-ATP synthase α belongs to the family of stress proteins HSP60. Currently, mounting evidences indicate F0F1-ATP synthase α may play a role in neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Recently, ATP synthase α was reported to have protective and therapeutic roles in primary cardiacmyocytes of iron-overloaded rats by lowering ROS production. However, little is understood about the role of ATP synthase α in cell death and neurodegeneration. Here, we demonstrate that overexpression of ATP synthase α suppresses huntingtin (htt) polyQ aggregation and toxicity in transfected SH-SY5Y cell lines. Overexpression of ATP synthase α is able to protect cell death caused by polyglutamine-expanded htt. Transient overexpression of ATP synthase α suppresses the aggregate formation by estimation of polyQ aggregation, Western blot analysis, and filter trap assay (FTA) in transfected SH-SY5Y cells. These results indicated that ATP synthase α has a strong inhibitory effect on polyglutamine aggregate formation and toxicity in vitro, and suggest a novel neuroprotective role of ATP synthase α.
DOI：
10.1073/pnas.0400243101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Lee, WCM;Yoshihara, M;Littleton, JT
通讯作者：
Littleton, JT
影响因子：
3.5
作者：
Cummings, CJ;Sun, YL;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
56.9
作者：
DiFiglia, M;Sapp, E;Aronin, N
通讯作者：
Aronin, N