食品科学 ›› 2018, Vol. 39 ›› Issue (17): 159-164.doi: 10.7506/spkx1002-6630-201817026

• 营养卫生 • 上一篇    下一篇

氨基甲酸乙酯诱导HepG2细胞凋亡的分子机制

刘会昌,石建新*   

  1. 上海交通大学生命科学技术学院,上海 200240
  • 出版日期:2018-09-15 发布日期:2018-09-18
  • 基金资助:
    国家重点基础研究发展计划(973计划)项目(2012CB72804)

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

LIU Huichang, SHI Jianxin*   

  1. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
  • Online:2018-09-15 Published:2018-09-18

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HepG2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HepG2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mRNA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mRNA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。

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

Abstract: 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.

Key words: ethyl carbamate, HepG2 cell, apoptosis, intrinsic pathway, endoplasmic reticulum stress, extrinsic pathway

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