X-irradiation reduces the proliferation of astrocytes by cell cycle arrest

X-irradiation reduces the proliferation of astrocytes by cell cycle arrest
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X 射线照射通过细胞周期停滞减少星形胶质细胞的增殖

DOI:
10.1016/j.neulet.2011.04.067
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发表时间:
2011-07
期刊:
Neuroscience Letters (IF 2.055)
影响因子:
--
通讯作者:
Zhou Zhu
Zhou Zhu
中科院分区:
其他
文献类型:
--
作者:
Qi Wang;Yi Xu;Zhou Zhu

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反应性星形胶质细胞增生是中枢神经系统损伤的细胞反应的关键组成部分之一,被认为是轴突再生的主要障碍。我们以前的研究表明,细胞周期抑制治疗可以减少体内星形胶质细胞的活化和增殖。在这项研究中,我们研究了是否反应性星形胶质细胞增生可以抑制X射线照射在体外通过调节细胞周期的进展。低剂量(4戈伊)X射线照射抑制星形胶质细胞增殖,BrdU和Ki 67免疫荧光染色显示星形胶质细胞单层培养和划痕损伤模型。4戈伊照射后12、24和48 h,BrdU(+)和Ki67(+)细胞比例均显著低于对照组。流式细胞仪分析表明,X射线照射后12和24 h,星形胶质细胞处于S期的比例呈剂量依赖性下降。此外,在X射线照射后,通过蛋白质印迹法观察到与对照星形胶质细胞培养物相比更高水平的p53。总之,这些数据支持X射线照射可以通过阻止细胞周期进程来减少星形胶质细胞增生,这可能构成以胶质细胞过度增殖为特征的疾病的有效治疗干预。
Reactive astrogliosis is one of the key components of the cellular response to CNS injury and is considered a major impediment to axonal regeneration. Our previous study demonstrated that cell cycle inhibition treatment can reduce astrocyte activation and proliferation in vivo. In this study, we examined whether reactive astrogliosis can be suppressed by X-irradiation in vitro by modulating cell cycle progression. X-irradiation with low dose (4 Gy) suppressed astrocyte proliferation as demonstrated by immunofluorescence staining with BrdU and Ki67 in monolayer astrocyte cultures and those in scratch-wound model. The proportions of BrdU (+) and Ki67 (+) cells at 12, 24, and 48 h after 4 Gy irradiation were significantly lower than those in control group. FACS analysis of monolayer astrocyte cultures showed that X-irradiation decreased the proportion of astrocytes in S phase at 12 and 24 h after irradiation with a dose-dependent manner. Furthermore, after X-irradiation, higher levels of p53 were observed by western blot as compared to control astrocyte cultures. Taken together, these data support that X-irradiation can decrease astrogliosis via arresting the cell cycle progression, which might constitute an effective therapeutic intervention in diseases characterized by excessive proliferation of glial cells.
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