RAC2-P38 MAPK-dependent NADPH oxidase activity is associated with the resistance of quiescent cells to ionizing radiation
RAC2-P38 MAPK-dependent NADPH oxidase activity is associated with the resistance of quiescent cells to ionizing radiation
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RAC2-P38 MAPK 依赖性 NADPH 氧化酶活性与静止细胞对电离辐射的抵抗力相关
DOI：
10.1080/15384101.2016.1259039
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Zhou, Guangming
中科院分区：
文献类型：
--
作者：
Pei, Hailong;Zhang, Jian;Zhou, Guangming
我们最近的研究表明，静止期G 0细胞比G1细胞对电离辐射更有抵抗力，然而，这种增加的辐射抵抗力的潜在机制尚不清楚。基于G 0细胞中诱导的相对较低的DNA损伤，我们假设这些细胞在暴露期间暴露于较少的氧化应激。Ras相关的C3肉毒毒素底物2（RAC 2）作为NADPH氧化酶的催化亚基，可能参与细胞对电离辐射的反应。在这里，我们表明，RAC 2在G 0细胞中表达水平较低，但在G1细胞中大幅增加。相对于G1期细胞，在G 0期细胞的总抗氧化能力增加后，暴露于X射线辐射，而细胞内的ROS和丙二醛浓度仅略有增加。X射线辐射诱导G1细胞DNA单链和双链断裂可被RAC 2基因敲低所抑制。P38 MAPK与RAC 2相互作用导致功能性RAC 2减少。G 0期细胞中P38 MAPK磷酸化水平的增加也增加了细胞的辐射抗性;然而，过量的ROS产生导致P38 MAPK去磷酸化。P38 MAPK、磷酸化P38 MAPK和RAC 2通过相互反馈和负反馈调节途径共同调节G 0细胞的辐射抗性。
ABSTRACT Our recent study showed that quiescent G0 cells are more resistant to ionizing radiation than G1 cells; however, the underlying mechanism for this increased radioresistance is unknown. Based on the relatively lower DNA damage induced in G0 cells, we hypothesize that these cells are exposed to less oxidative stress during exposure. As a catalytic subunit of NADPH oxidase, Ras-related C3 botulinum toxin substrate 2 (RAC2) may be involved in the cellular response to ionizing radiation. Here, we show that RAC2 was expressed at low levels in G0 cells but increased substantially in G1 cells. Relative to G1 cells, the total antioxidant capacity in G0 phase cells increased upon exposure to X-ray radiation, whereas the intracellular concentration of ROS and malondialdehyde increased only slightly. The induction of DNA single- and double-stranded breaks in G1 cells by X-ray radiation was inhibited by knockdown of RAC2. P38 MAPK interaction with RAC2 resulted in a decrease of functional RAC2. Increased phosphorylation of P38 MAPK in G0 cells also increased cellular radioresistance; however, excessive production of ROS caused P38 MAPK dephosphorylation. P38 MAPK, phosphorylated P38 MAPK, and RAC2 regulated in mutual feedback and negative feedback regulatory pathways, resulting in the radioresistance of G0 cells.