The role of protein kinase C alpha translocation in radiation-induced bystander effect.
The role of protein kinase C alpha translocation in radiation-induced bystander effect.
复制标题
蛋白激酶Cα易位在辐射诱导的旁观者效应中的作用
DOI：
10.1038/srep25817
复制
发表时间：
2016-05-11
影响因子：
4.6
通讯作者：
Hong M
中科院分区：
文献类型：
--
作者：
Fang Z;Xu A;Wu L;Hei TK;Hong M
电离辐射是一种众所周知的人类致癌物质。过去十年积累的证据表明，核内/细胞外靶点和事件也可能在调节电离辐射生物反应方面发挥关键作用。然而，辐射诱导的旁观者效应的潜在机制仍不清楚。在当前的研究中，用α粒子照射AL细胞，并研究旁观者细胞的反应。我们发现，在旁观者AL细胞中，蛋白激酶C α（PKCα）从胞浆转移到膜组分。用PKC转位抑制剂chelerythrine chloride预处理细胞可抑制诱导的细胞外信号调节激酶（ERK）活性和增加的环氧化酶2（考克斯-2）表达以及旁观者细胞的致突变效应。此外，肿瘤坏死因子α（TNFα）在直接照射而不是旁观者细胞中升高;而TNFα受体1（TNFR 1）在旁观者细胞的膜部分中增加。进一步的分析表明，PKC激活导致TNFR 1的加速内化和再循环。我们的数据表明，PKCα易位可能作为辐射诱导的旁观者反应的早期事件发生，并介导TNFα诱导的信号通路，导致ERK激活和考克斯-2上调。
Ionizing radiation is a well known human carcinogen. Evidence accumulated over the past decade suggested that extranuclear/extracellular targets and events may also play a critical role in modulating biological responses to ionizing radiation. However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear. In the current study, ALcells were irradiated with alpha particles and responses of bystander cells were investigated. We found out that in bystander ALcells, protein kinase C alpha (PKCα) translocated from cytosol to membrane fraction. Pre-treatment of cells with PKC translocation inhibitor chelerythrine chloride suppressed the induced extracellular signal-regulated kinases (ERK) activity and the increased cyclooxygenase 2 (COX-2) expression as well as the mutagenic effect in bystander cells. Furthermore, tumor necrosis factor alpha (TNFα) was elevated in directly irradiated but not bystander cells; while TNFα receptor 1 (TNFR1) increased in the membrane fraction of bystander cells. Further analysis revealed that PKC activation caused accelerated internalization and recycling of TNFR1. Our data suggested that PKCα translocation may occur as an early event in radiation-induced bystander responses and mediate TNFα-induced signaling pathways that lead to the activation of ERK and up-regulation of COX-2.