Role of the MAPK pathway in the observed bystander effect in lymphocytes co-cultured with macrophages irradiated with γ-rays or carbon ions
Role of the MAPK pathway in the observed bystander effect in lymphocytes co-cultured with macrophages irradiated with γ-rays or carbon ions
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MAPK 通路在观察到的淋巴细胞与巨噬细胞经 γ 射线或碳离子照射的旁观者效应中的作用
DOI：
10.1016/j.lfs.2015.02.017
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发表时间：
2015-04-15
期刊：
影响因子：
6.1
通讯作者：
Shao, Chunlin
中科院分区：
文献类型：
--
作者：
Dong, Chen;He, Mingyuan;Shao, Chunlin
目的：辐射诱导的旁观者效应(RIBE)对空间粒子辐射的癌症风险有潜在的影响；然而，RIBE背后的机制尚不清楚。研究MAPK通路在不同线性能量转移(LET)中的作用。主要方法：用伽玛射线或碳离子照射人巨噬细胞U937细胞，然后与未照射的HMy2.CIR(HMY)淋巴细胞共培养不同时间。检测照射后U937细胞MAPK蛋白的活化及细胞内一氧化氮(NO)和活性氧(ROS)的产生。用HMY细胞微核形成来评价旁观者的损伤。一些U937细胞在照射前用不同的MAPK抑制剂进行处理。主要发现：与照射后的U937细胞共培养后，HMY细胞中有额外的MN形成，这种旁观者MN的形成依赖于伽玛射线照射共培养的时间，但在与碳照射共培养1h后，这种旁观者MN的形成仍然很高。进一步的研究表明，RIBES的时间响应与LET有关，在RIBES中，ERK通过调节旁观者信号因子NO和ROS的产生，在调节RIBES方面扮演着不同于JNK和p38的角色。重要的是：高LET辐射的RIBE持续时间可能比伽马射线长得多，这意味着太空飞行中的粒子辐射可能有很高的长期有害影响风险。针对MAPK通路的适当干预可能在降低这种风险方面具有重要意义。(C)2015 Elsevier Inc.保留所有权利。
Aims: The radiation-induced bystander effect (RIBE) has potential implications in cancer risks from space particle radiation; however, the mechanisms underlying RIBE are unclear. The role of the MAPK pathway in the RIBEs of different linear energy transfer (LET) was investigated.Main methods: Human macrophage U937 cells were irradiated with gamma-rays or carbon ions and then co-cultured with nonirradiated HMy2.CIR (HMy) lymphocytes for different periods. The activation of MAPK proteins and the generation of intracellular nitric oxide (NO) and reactive oxygen species (ROS) in the irradiated U937 cells were measured. Micronuclei (MN) formation in the HMy cells was applied to evaluate the bystander damage. Some U937 cells were pretreated with different MAPK inhibitors before irradiation.Key findings: Additional MN formation was induced in the HMy cells after co-culturing with irradiated U937 cells, and the yield of this bystander MN formation was dependent on the co-culture period with gamma-ray irradiation but remained high after 1 h of co-culture with carbon irradiation. Further investigations disclosed that the time response of the RIBEs had a relationship with LET, where ERK played a different role from JNK and p38 in regulating RIBEs by regulating the generation of the bystander signaling factors NO and ROS.Significance: The finding that the RIBE of high-LET radiation could persist for a much longer period than that of gamma-rays implies that particle radiation during space flight could have a high risk of long-term harmful effects. An appropriate intervention targeting the MAPK pathway may have significant implications in reducing this risk. (C) 2015 Elsevier Inc. All rights reserved.