PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice
PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice
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DOI：
10.1016/j.bbrc.2011.12.098
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发表时间：
2012-02-03
影响因子：
3.1
通讯作者：
Cerchiaro, Giselle
中科院分区：
文献类型：
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作者：
Bertuchi, Fernanda R.;Bourgeon, Dominique M. G.;Cerchiaro, Giselle
PrPC蛋白尤其存在于神经系统细胞的细胞膜上，因其有争议的抗氧化活性而被广泛研究。在这项研究中，我们阐明了纯化的小鼠PrPc在溶液中清除自由基的活性，以及它作为细胞保护剂参与了氧化剂处理的星形胶质细胞。在体外和使用EPR自旋捕获技术，我们观察到PrPC减少了Fenton反应体系(Cu2+/抗坏血酸/H_2O_2)中DMPO陷阱的氧化，这表明这一点大约减少了DMPO/OH的70%。在培养的PrPC基因敲除的小鼠星形胶质细胞中，PrPC的缺失导致在H_2O_2处理的前3小时细胞内ROS(活性氧物种)的产生增加。这种ROS的快速增加扰乱了PrPC基因敲除的星形胶质细胞的细胞周期，与培养的野生型星形胶质细胞相比，这增加了处于亚G1期的细胞数量。我们得出结论，PrPC在溶液中起着自由基清除剂的作用，在星形胶质细胞中，它对于保护免受外部化学物质引起的氧化应激是必不可少的，这是人类神经退行性中枢神经系统疾病和缺血等病理条件下的一种可能情况。(C)2011 Elsevier Inc.保留所有权利。
The PrPC protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrPc in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrPC decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu2+/ascorbate/H2O2), which was demonstrated by approximately 70% less DMPO/OH. In cultured PrPC-knockout astrocytes from mice, the absence of PrPC caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H2O2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrPC-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrPC in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia. (C) 2011 Elsevier inc. All rights reserved.