氨基甲酸乙酯诱导HepG2细胞凋亡的分子机制  

Molecular Mechanisms of Ethyl Carbamate-Induced Apoptosis in Human HepG2 Cells

作　　者：刘会昌[1] 石建新[1] LIU Huichang;SHI Jianxin(School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]上海交通大学生命科学技术学院,上海200240

出　　处：《食品科学》2018年第17期159-164,共6页Food Science

基　　金：国家重点基础研究发展计划(973计划)项目(2012CB72804)

摘　　要：发酵食品中的氨基甲酸乙酯(ethyl carbamate,EC)是国际癌症研究机构认可的2A类可能致癌物。前期研究表明EC可诱导人类Hep G2细胞凋亡,但机理未明。本研究采用实时荧光定量聚合酶链式反应和蛋白免疫印迹技术检测100 mmol/L EC处理对Hep G2细胞凋亡通路基因的影响,以探索EC诱导人体细胞凋亡的分子机制。结果表明:4 h EC处理在促进诱骗受体基因TNFRSF10D和促存活基因GADD45B表达的同时,激活细胞凋亡相关的线粒体介导的内源通路和内质网应激通路基因的表达,EC对绝大多数受试基因的m RNA水平和蛋白水平的影响一致。12 h EC处理显著提高凋亡相关基因的m RNA水平,同时显著降低大多数基因的蛋白表达水平,表明长时间EC处理抑制了细胞内蛋白的合成。本研究结果为食源性EC的进一步风险评估提供了依据。Ethyl carbamate(EC)that is commonly found in fermented foods is regarded as a Group 2A carcinogen by the International Agency for Research on Cancer.Our previous study indicated that EC could induce apoptosis in human HepG2 cells;however,its molecular mechanisms remain unclear.In this study,we aim to explore the molecular mechanisms of EC-induced apoptosis in HepG2 cells using real-time quantitative PCR and Western blotting to examine the effects of 100 mmol/L EC treatment on the expression of apoptosis-related genes at both the mRNA and protein levels.The results showed that 4 h EC treatment increased the mRNA and protein levels of decoy receptor(TNFRSF10D),pro-survival(GADD45B),and apoptosis-related gene from the mitochondria mediated intrinsic and endoplasmic reticulum stress response pathways.In addition,12 h EC treatment up-regulated significantly the mRNA levels of apoptosis-related genes,but down-regulated significantly the protein levels of most tested genes,indicating that long-term EC treatment can inhibit protein synthesis.This study can lay a solid foundation for further risk assessment of food-borne EC.

关 键 词：氨基甲酸乙酯 HEPG2细胞 细胞凋亡 内源途径 内质网氧化应激 外源途径 

分 类 号：TS201.6[轻工技术与工程—食品科学]