VCP在1.8GHz微波辐射对人晶状体上皮细胞作用后的生物学效应及其机制

Daily exposure to radiofrequency electromagnetic fields (RF EMF) from mobile phones has raised public concerns on human health. Human lens are mobile phone radiation target organs due to its accommodation in eyes of easier exposure to the radiation and special structure with fully water-soluble proteins to absorb radiation. Previous studies have shown that mobile phone radiation induces reversible biological effects in human lens epithelial cells, including cellular DNA damages, but it remains to be elucidated that how does mobile phone radiation induces cellular bio-effects and what are the mechanisms of cellular response to the radiation. To answer this question, we have conducted a project supported by a NSFC grant to screen mobile phone radiation responsive proteins in LECs and identified VCP, a key actor in the interplay between autophagy and ubiquitin/proteasome catabolic pathways, as a responsive protein; however, the role of VCP in mobile phone radiation induced bio-effects is not clear. In the present study, we will 1) examine the biological consequences of mobile phone radiation induced up-regulation of VCP in LECs, 2) investigate how mobile phone radiation affect VCP activity and its underlying mechanism, 3) evaluate the role of VCP inhibitor in mobile phone radiation induced bio-effects. This study will shed light on the mechanism of mobile phone radiation induced bio-effects in LECs and the role of VCP in cellular response to mobile phone radiation, and may provide a novel protective strategy against mobile phone radiation with VCP inhibitor.

移动手机辐射对人体健康的危害越来越引起人们的重视。眼晶状体靠近移动电话辐射的部位，且含水量高（易于吸收微波辐射的能量）、无血管（组织散热慢），是人体组织中对电磁辐射的靶器官。研究显示微波辐射可导致人晶状体上皮细胞（LECs）产生一系列的可逆性损伤与抗损伤修复，但细胞如何激活其抗损伤修复系统、降解错误折叠蛋白的机制尚不清楚。基于前期鸟枪法质谱分析后发现微波辐射上调蛋白降解和细胞自噬调节关键因子VCP的表达，本项目拟进一步分析手机辐射上调VCP蛋白介导的蛋白降解、细胞自噬等后续生物学效应，探索VCP在微波辐射作用于人LECs中的机制，在此基础上，分析VCP抑制剂对手机辐射致人LECs生物学效应的干预作用。本项目研究将有助于阐明手机辐射致人晶状体上皮细胞可逆性损伤及其修复机制，并可能为研发抗手机辐射致人晶状体损伤的防护手段提供实验基础。

前期研究显示微波辐射可导致人晶状体上皮细胞（LECs）产生一系列的可逆性损伤与抗损伤修复，我们前期研究已发现1.8 GHz微波辐射人LECs后可致遗传毒性、影响细胞增殖等效应，同时细胞内多种蛋白被激活，从而产生自我修复的细胞活动，但具体的机制不明。本课题组应用蛋白质谱、qRT-PCR、western blot等技术和方法深入研究发现：（1）1.8 GHz 微波辐射可导致人LECs蛋白质表达谱发生改变，VCP，USP35和SRP68为辐照后产生的特异性蛋白，其中VCP和USP35为泛素-蛋白酶体系的重要蛋白，参与保持细胞内蛋白平衡，维持细胞正常功能；（2）成功建立细胞自噬模型，探究人LECs在氧化应激下的自噬现象，为晶状体上皮细胞的氧化损伤保护提供可靠的实验依据和研究基础。