亚砷酸钠诱导的活性氧增加人皮肤细胞N^6-甲基腺苷水平  

Reactive oxygen species induced by sodium arsenite increases N^6-methyladenosine modification in human keratinocyte cells

作　　者：赵田禾 李欣洋 孙东雷 张遵真 ZHAO Tian-he;LI Xin-yang;SUN Dong-lei;ZHANG Zun-zhen(West China School of Public Health,Sichuan University,Chengdu Sichuan 610041,China)

机构地区：[1]四川大学华西公共卫生学院(华西第四医院),四川成都610041

出　　处：《现代预防医学》2019年第6期1074-1078,共5页Modern Preventive Medicine

基　　金：国家自然科学基金(项目编号:81773380)

摘　　要：目的探究亚砷酸钠诱导的活性氧是否影响N^6-甲基腺苷(m^6A)水平,从RNA表观遗传学角度探讨亚砷酸钠的毒性机制。方法以亚砷酸钠作为活性氧诱导剂,以N-乙酰半胱氨酸作为活性氧清除剂,检测细胞在亚砷酸钠单独处理和亚砷酸钠联合N-乙酰半胱氨酸处理情况下皮肤细胞活性氧积累情况,同时测定m^6A及其甲基化酶的m RNA和蛋白水平的改变。结果在5、10和15μM的亚砷酸钠处理下,活性氧含量随砷浓度升高而增加;在亚砷酸钠染毒浓度为15μM时,细胞内总m^6A水平水平相比于对照组升高了1.49倍(P<0.05),m^6A甲基化酶(METTL3、METTL14和WTAP)m RNA表达水平相应升高(P<0.05),METTL14和WTAP蛋白表达水平分别为对照组的1.47倍和1.85倍(P<0.05)。N-乙酰半胱氨酸可以降低异常升高的活性氧、m^6A以及其甲基化酶水平。结论亚砷酸钠诱导的活性氧能增加人皮肤细胞m^6A的修饰水平,其机制可能与上调m^6A甲基化酶表达水平有关。Objective The aim of this study was to explore whether reactive oxygen species(ROS)induced by sodium arsenite affect N6-methyladenosine(m6A)level,in order to provide a new idea for the study on toxicity induced by arsenite from the perspective of RNA epigenetics.Methods Arsenite was used to induce ROS,and N-acetylcysteine was used to eliminate ROS.ROS level,mRNA and protein levels of m6A and its methylases(METTL3,METTL14,and WTAP)were tested in arsenite treatment group and arsenite combined with N-acetylcysteine treatment group.Results 5,10 and 15 μM of arsenite elevated ROS level in a concentration-dependent manner.With the treatment of 15 μM arsenite,the m^6A level increased 1.49-fold compared to the control(P<0.05),the RNA levels of m6A methylases(METTL3,METTL14 and WTAP)elevated(P<0.05),and the protein levels of METTL14 and WTAP were increased 1.47-fold and 1.85-fold compared to the control,respectively(P<0.05).N-acetylcysteine could suppress abnormal increase of m6A and its methylases levels in HaCaT cells treated by arsenite.Conclusion ROS induced by arsenite increases m^6A level possibly via upregulation of m6A methylases.

关 键 词：N^6-甲基腺苷 亚砷酸钠 活性氧 人皮肤细胞 

分 类 号：R181.24[医药卫生—流行病学]