Efficient production of reactive oxygen species in neural precursor cells after exposure to 250 MeV protons

Efficient production of reactive oxygen species in neural precursor cells after exposure to 250 MeV protons
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DOI:
10.1667/rr3369.1
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发表时间:
2005-10-01
期刊:
影响因子:
3.4
通讯作者:
Limoli, CL
Limoli, CL
中科院分区:
医学3区
文献类型:
--
作者:
Giedzinski, E;Rola, R;Limoli, CL

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空间辐射环境由高能离子组成,其中质子占主导地位,对宇航员构成一系列潜在的健康风险。这些颗粒穿过某些组织可能会损害敏感细胞的活力和/或功能,包括海马齿状颗粒下区中发现的神经前体。辐射已被证明在体内耗尽这些细胞,并且这些关键细胞的减少被认为会损害神经发生和认知。为了更全面地了解这些前体细胞在辐照后的行为机制,我们开发了一种体外神经前体细胞系统,并使用它来评估暴露于250 MeV的Braggpeak质子后ROS和线粒体终点的急性(0-48 h)变化。相对活性氧水平增加,几乎所有剂量(1-10戈伊)和postirradiation时间(6-24小时)相比,未照射的控制。质子照射后ROS的增加比X射线观察到的更快,并在6和24小时显示出明确的剂量反应,每格分别增加约10%和3%。然而,48小时后辐射,ROS水平低于控制和符合线粒体轻微减少!内容使用抗氧化剂α-硫辛酸(照射前或照射后)可以消除辐射诱导的ROS水平升高。我们的研究结果证实了早期使用X射线的研究,并提供了进一步的证据表明,ROS升高是神经前体细胞放射反应的组成部分。(c)2005年,辐射研究协会。
The space radiation environment is composed of highly energetic ions, dominated by protons, that pose a range of potential health risks to astronauts. Traversals of these particles through certain tissues may compromise the viability and/or function of sensitive cells, including neural precursors found within the dentate subgranular zone of the hippocampus. Irradiation has been shown to deplete these cells in vivo, and reductions of these critical cells are believed to impair neurogenesis and cognition. To more fully understand the mechanisms underlying the behavior of these precursor cells after irradiation, we have developed an in vitro neural precursor cell system and used it to assess acute (0-48 h) changes in ROS and mitochondrial end points after exposure to Braggpeak protons of 250 MeV. Relative ROS levels were increased at nearly all doses (1-10 Gy) and postirradiation times (6-24 h) compared to unirradiated controls. The increase in ROS after proton irradiation was more rapid than that observed with X rays and showed a well-defined dose response at 6 and 24 h, increasing approximately 10% and 3% per gray, respectively. However, by 48 h postirradiation, ROS levels fell below controls and coincided with minor reductions in mitochondria! content. Use of the antioxidant a-lipoic acid (before or after irradiation) was shown to eliminate the radiation-induced rise in ROS levels. Our results corroborate earlier studies using X rays and provide further evidence that elevated ROS are integral to the radioresponse of neural precursor cells. (c) 2005 by Radiation Research Society.