Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis
Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis
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DOI：
10.1016/j.fct.2017.05.028
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发表时间：
2017-08-01
影响因子：
4.3
通讯作者：
Lampen, Alfonso
中科院分区：
文献类型：
--
作者：
Buhrke, Thorsten;Schultrich, Katharina;Lampen, Alfonso
3-氯-1，2-丙二醇（3-MCPD）及其异构体2-氯-1，3-丙二醇（2-MCPD）是存在于含油脂食品中的热诱导食品污染物。肾脏和睾丸是3-MCPD的主要靶器官。几乎没有关于2-MCPD毒性的数据。在此，通过肾脏、肝脏和睾丸的微阵列分析，对大鼠重复暴露于每天10 mg/kg体重的无毒剂量2-MCPD或3-MCPD 28天后的转录组学反应进行了表征。3-MCPD在所有器官中的作用均比2-MCPD明显。数据集之间的有限重叠表明，2-MCPD和3-MCPD不具有相同的毒性分子机制。通过将转录组学数据与3-MCPD对蛋白质组学调节的数据集相结合，开发了关于3-MCPD诱导的葡萄糖利用和氧化应激反应调节的全面观点。生物信息学分析显示，Nrf 2（核因子（红细胞衍生2）样2）信号可能参与介导对3-MCPD的氧化应激反应。总之，这项研究首次提供了两种重要食品污染物2-MCPD和3-MCPD改变全球基因表达的数据。数据表明，这两种化合物的影响之间存在深刻的差异，并大大拓宽了我们对3-MCPD诱导的葡萄糖利用和氧化还原平衡紊乱的分子细节的了解。(C)2017爱思唯尔有限公司版权所有
3-Chloro-1,2-propanediol (3-MCPD) and its isomer 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants present in oil- and fat-containing foodstuff. Kidney and testes are among the main target organs of 3-MCPD. Almost no data on 2-MCPD toxicity are available. Here, transcriptomic responses following repeated-dose exposure of rats to non-toxic doses of 10 mg/kg body weight per day 2-MCPD or 3-MCPD for 28 days were characterized by microarray analysis of kidney, liver, and testes. 3-MCPD exerted more pronounced effects than 2-MCPD in all organs. The limited overlap between the datasets indicates that 2-MCPD and 3-MCPD do not share the same molecular mechanisms of toxicity. By combining transcriptomic data with datasets on proteomic regulation by 3-MCPD, a comprehensive view on 3-MCPD-induced regulation of glucose utilization and oxidative stress response was developed. Bioinformatic analyses revealed that Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling is likely to be involved in mediating the oxidative stress response to 3-MCPD. In summary, this study for the first time presents data on alterations in global gene expression by two important food contaminants, 2-MCPD and 3-MCPD. Data demonstrate profound differences between the effects of the two compounds and substantially broaden our knowledge on molecular details of 3-MCPD-induced disturbance of glucose utilization and redox balance. (C) 2017 Elsevier Ltd. All rights reserved.