纳米二氧化锆对人永生化角质形成细胞组蛋白H3修饰的影响  

Effects of Zirconium Dioxide Nanoparticles Exposure on Histone H3 Modification in Human Skin Keratinocytes

作　　者：赵晓旭 姚燕坊 侯巧利 ZHAO Xiao-Xu;YAO Yan-Fang;HOU Qiao-Li(Provincial Key Laboratory of Ecology-Toxicological Effects and Control for Emerging Contaminants,Putian 351100,China;Key Laboratory of Ecological Environment and Information Atlas Fujian Provincial University,Putian 351100,China;College of Environmental and Biological Engineering,Putian University,Putian 351100,China;College of Environment and Safety Engineering,Fuzhou University,Fuzhou 350108,China)

机构地区：[1]福建省新型污染物生态毒理效应与控制重点实验室,莆田351100 [2]生态环境及其信息图谱福建省高等学校重点实验室,莆田351100 [3]莆田学院环境与生物工程学院,莆田351100 [4]福州大学环境与安全工程学院,福州350108

出　　处：《生物化学与生物物理进展》2023年第8期1959-1970,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31801462);福建省自然科学基金(2021J011105,2020J05211);莆田学院引进人才科研启动项目(2018055)资助。

摘　　要：目的阐明纳米二氧化锆暴露对人永生化角质形成细胞HaCaT组蛋白H3常见修饰位点的影响,探讨组蛋白H3修饰变化的潜在机制,为纳米材料的进一步安全应用提供理论基础。方法在利用扫描电子显微镜、激光粒度仪、X射线衍射仪等技术对纳米二氧化锆进行详细表征的基础上,通过蛋白质免疫印迹及流式细胞术等方法评价纳米二氧化锆暴露对细胞生存率、细胞内蓄积量以及组蛋白H3修饰等的影响。结果在分散介质中纳米二氧化锆明显团聚,比表面积减少,二次粒径增大,其短时间内(1 h)即诱导了组蛋白H3第10位丝氨酸的磷酸化、第9及14位赖氨酸的乙酰化、第4及27位赖氨酸的三甲基化修饰水平的升高。进一步分析发现,纳米二氧化锆的细胞内蓄积量及其引起的DNA损伤水平,与纳米二氧化锆诱导的组蛋白H3修饰水平均呈线性相关。结论纳米二氧化锆暴露后诱导了HaCaT细胞组蛋白H3常见修饰位点的变化,其细胞内的蓄积是诱导组蛋白H3修饰变化的关键因素之一,且组蛋白H3修饰的调控机制可能涉及DNA损伤修复途径。Objective The effects of zirconium dioxide nanoparticles(ZrO_(2)-NPs)exposure on the histone H3 modification in human skin keratinocytes(HaCaT)were clarified,and the underlying mechanism of histone H3 modification changes was explored in this study to provide a theoretical basis for the further safe application of nanomaterials.Methods The ZrO_(2)-NPs were firstly characterized in detail by means of scanning electron microscope,laser particle size analyzer,X-rad diffraction,etc.Subsequently,the effects of ZrO_(2)-NPs exposure on the cell viability,intracellular accumulation and histone H3 modification were evaluated by Western blotting and flow cytometry.Results The results showed that ZrO_(2)-NPs after dispersion treatment exhibited obvious agglomeration,and their specific surface area decreased whereas the secondary particle size increased.The phosphorylation of histone H3 at serine 10,the acetylation of histone H3 at lysine 9 and 14,the trimethylation of histone H3 at lysine 4 and 27 were induced to upregulate by ZrO_(2)-NPs in a short time(1 h).Through further analysis,it was found that the intracellular accumulation of ZrO_(2)-NPs and the level of DNA damage caused by ZrO_(2)-NPs were linearly correlated with the level of histone H3 modification induced by ZrO_(2)-NPs.Conclusion These results suggested that the changes of the common modification sites of histone H3 in HaCaT cells were induced after exposure of ZrO_(2)-NPs.The intracellular accumulation of ZrO_(2)-NPs is one of the key factors in its induction of changes in histone H3 modification,and regulation mechanism of histone H3 modification may be involved in DNA damage repair pathways.

关 键 词：纳米二氧化锆 表观遗传学 组蛋白修饰 细胞内蓄积 DNA损伤 

分 类 号：Q23[生物学—细胞生物学]