赭曲霉毒素A对HEK293细胞DNA和组蛋白甲基化修饰酶的影响  

Effects of OTA on global DNA methylation and histone methylation modifying enzymes in HEK293 cells

作　　者：李晓红[1] 罗红霞[1] 句荣辉[1] 李淑荣[1] 王丽[1] 谌小立[2] LI Xiaohong;LUO Hongxia;JU Ronghui;LI Shurong;WANG Li;SHEN Xiaoli(Beijing Agricultural Vocational College,Beijing 102442,China;School of Public Health,Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]北京农业职业学院,北京102442 [2]遵义医学院公共卫生学院,贵州遵义563000

出　　处：《河南农业大学学报》2018年第5期759-764,共6页Journal of Henan Agricultural University

基　　金：国家自然科学基金项目(31460426);北京农业职业学院院级项目(XY-YT-16-44);北京市科技计划项目(20160202-14);贵州省科学技术基金项目(黔科合LH字[2014]7546号);遵义医学院优秀青年人才项目(17zy-006);遵义医学院博士学位授权支撑学科建设经费项目(2015-0996036)

摘　　要：探讨了赭曲霉毒素A(Ochratoxin A,OTA)诱导HEK293细胞整体基因组DNA甲基化和组蛋白H3K9甲基转移酶活性变化的剂量效应及可能的调控机制。结果表明,OTA抑制了HEK293细胞的生长,降低了整体基因组DNA甲基化水平,并呈剂量效应关系。随OTA暴露剂量的增加,DNA甲基化转移酶DNMT1 mRNA表达量降低。且本研究首次探究了OTA对组蛋白H3K9甲基化修饰酶的影响。结果显示,OTA引起组蛋白H3K9甲基转移酶活性升高,且H3K9甲基化修饰酶G9a和SETDB1 mRNA表达量在高剂量OTA暴露时显著升高。OTA可能分别通过调控DNMT1、G9a及SETDB1使整体基因组DNA甲基化水平降低和H3K9甲基转移酶活性升高,这可能是OTA导致肾毒性的表观遗传机制。An investigation was coducted on the effects of Ochratoxin A(OTA)on global DNA methylation and the activity of H3K9 histone methyltransferase(HMT),and regulation mechanism of chromatin modifying enzymes in human embryonic kidney cells(HEK293).The results showed that OTA inhibited cell proliferation and decreased the global DNA methylation in a dose-independent manner.The downregulation of DNA methyltransferases(DNMT1)mRNA expression in HEK293 cells was also observed which the first time to research the effect of OTA on the histone 3 lysine 9 modifications.The results indicated that OTA increased the the activity of HMTs and the mRNA expression of G9a and SETDB1.This study showed that OTA may reduce the global DNA methylation level by regulating DNMT1 and increase the HMTs activity by regulating G9a and SETDB1,which may be the epigenetic mechanism of OTA induced nephrotoxicity.

关 键 词：赭曲霉毒素A HEK293细胞 DNA甲基化 H3K9甲基化 组蛋白修饰酶 

分 类 号：TS201[轻工技术与工程—食品科学]