Inactivation of ataxia telangiectasia mutated gene can increase intracellular reactive oxygen species levels and alter radiation-induced cell death pathways in human glioma cells
Inactivation of ataxia telangiectasia mutated gene can increase intracellular reactive oxygen species levels and alter radiation-induced cell death pathways in human glioma cells
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DOI：
10.3109/09553002.2011.538128
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发表时间：
2011-04-01
影响因子：
2.6
通讯作者：
Chiang, Chi-Shiun
中科院分区：
文献类型：
--
作者：
Wang, Shu-Chi;Wu, Chu-Chiao;Chiang, Chi-Shiun
目的：为探讨共济失调毛细血管扩张突变（ATM）调控的活性氧（ROS）和细胞死亡途径对U87 MG胶质瘤细胞电离辐射（IR）和氧化应激反应的影响，采用小分子干扰RNA（siRNA）技术阻断U87 MG胶质瘤细胞ATM表达。结果：阻断ATM表达可增加U87 MG细胞内ROS水平，增加细胞对IR和氧应激的敏感性;抗氧化剂N-乙酰半胱氨酸（NAC）可以部分抵消这种影响。ATM的敲除使得细胞在IR暴露后不能修复亚致死或潜在致死的损伤和DNA双链断裂（DSB）; NAC不能抵消这一点。ATM没有控制的途径，一个细胞用于死亡后IR，这似乎是ROS dependent.Conclusion：ATM参与氧化还原控制，但ROS升高后ATM敲低似乎更多地参与决定什么细胞死亡途径是利用后IR比DSB修复和放射敏感性。
Purpose: To investigate the effects of ataxia telangiectasia mutated (ATM)-regulated reactive oxygen species (ROS) and cell death pathways on the response of U87MG glioma cells to ionising radiation (IR) and oxidative stress.Material and methods: ATM expression was blocked in U87MG glioma cells using a small interfering RNA (siRNA) technique. Cell survival, sub-lethal damage (SLD), and potential lethal damage (PLD) repair following IR were assessed by clonogenic assay while changes in intracellular ROS, the apoptosis, and autophagy were followed by flow cytometry and Western blotting.Results: Blocking ATM expression in U87MG cells increased intracellular ROS levels and sensitivity to the cytotoxic effects of IR and oxygen stress; effects that could be partly counteracted by the antioxidant N-acetylcysteine (NAC). Knock down of ATM rendered cells unable to repair sub-lethal or potentially lethal damage and DNA double strand breaks (DSB) after IR exposure; something that NAC could not counteract. ATM did control the pathways a cell used to die following IR and this did seem to be ROS-dependent.Conclusion: ATM is involved in redox control but ROS elevations following ATM knock down seem more involved in the decision as to what cell death pathway is utilised after IR than DSB repair and radiosensitivity.