3-Monochloro-1,2-propanediol (3-MCPD) induces apoptosis via mitochondrial oxidative phosphorylation system impairment and the caspase cascade pathway
3-Monochloro-1,2-propanediol (3-MCPD) induces apoptosis via mitochondrial oxidative phosphorylation system impairment and the caspase cascade pathway
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3-一氯-1,2-丙二醇 (3-MCPD) 通过线粒体氧化磷酸化系统损伤和 caspase 级联途径诱导细胞凋亡
DOI：
10.1016/j.tox.2016.09.017
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发表时间：
2016-11-30
期刊：
影响因子：
4.5
通讯作者：
Xia, Xiaodong
中科院分区：
文献类型：
--
作者：
Peng, Xiaoli;Gan, Jing;Xia, Xiaodong
3-一氯-1,2-丙二醇（3-MCPD）是食品中毒性最强的氯丙醇化合物，主要在热加工过程中产生。肾脏是 3-MCPD 的主要靶器官之一。使用人胚胎肾细胞 (HEK293FT) 作为体外模型，通过染料摄取、乳酸脱氢酶 (LDH) 泄漏和 MTT 测定评估，我们发现 3-MCPD 导致细胞毒性浓度依赖性增加。 3-MCPD处理的HEK293FT细胞线粒体膜电位降低，线粒体氧化磷酸化系统受损，特别是电子传递链复合物II、复合物IV、复合物III的mRNA表达量和蛋白合成量减少。更重要的是，由于 ATP 合酶（ATP6 和 ATP8）表达下调，以及 ATP 合成所需的跨膜电位丧失，3-MCPD 显着抑制能量释放（ATP 合成）。线粒体凋亡因子 Bax/Bcl-2 比例下降，细胞色素 C 从线粒体释放到细胞质中，随后激活凋亡启动子 caspase 9 和凋亡执行器（caspase 3、caspase 6 和 caspase 7），导致细胞凋亡。 caspase 8和caspase 2的激活表明可能还有其他因素诱导caspase依赖性细胞凋亡。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
3-Monochloro-1,2-propanediol (3-MCPD) is the most toxic chloropropanols compounds in foodstuff which mainly generated during thermal processing. Kidney is one of the primary target organs for 3-MCPD. Using human embryonic kidney cell (HEK293FT) as an in vitro model, we found that 3-MCPD caused concentration-dependent increase in cytoxicity as assessed by dye uptake, lactatedehydrogenase (LDH) leakage and MTT assays. HEK293FT cell treated with 3-MCPD suffered the decrease of mitochondrial membrane potential and the impairment of mitochondrial oxidative phosphorylation system, especially the reduced amount of mRNA expression and protein synthesis of electron transport chain complex II, complex IV, and complex III. More importantly, energy release (ATP synthesis) was significantly inhibited by 3-MCPD resulting from the down regulation expressions of ATP synthase (ATP6 and ATP8), as well as the loss of transmembrane potential required for synthesis of ATP. The decreased ratio of mitochondrial apoptogenic factors Bax/Bcl-2 and the cytochrome-c release from mitochondria to cytosol followed by the activation of apoptotic initiators caspase 9 and apoptotic executioners (caspase 3, caspase 6 and caspase 7) leading to apoptosis. The activation of caspase 8 and caspase 2 implied that there were probably other factors to induce the caspase-dependent apoptosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.