Global DNA hypomethylation: A potential mechanism in King pigeon nerve tissue damage induced by avermectin
Global DNA hypomethylation: A potential mechanism in King pigeon nerve tissue damage induced by avermectin
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DOI：
10.1016/j.cbi.2014.05.004
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发表时间：
2014-08-05
影响因子：
5.1
通讯作者：
Xu, Shi-wen
中科院分区：
文献类型：
--
作者：
Cao, Ye;Chen, Li-jie;Xu, Shi-wen
阿维菌素（AVM）作为一种高效的杀虫杀线虫剂，已广泛应用于农业生产和畜牧业生产中。因此，动物粪便中的反车辆地雷残留物或其活性代谢物对环境中的非目标生物构成毒性威胁。DNA甲基化作为最具特征的表观遗传现象，是环境化学毒物毒性评价的重要生物学信号。本研究分析了亚慢性暴露后鸽脑组织基因组DNA甲基化的总体水平，以及DNA甲基转移酶（DNMTs）和去甲基化酶甲基-CpG结合域蛋白2（MBD 2）的表达水平（AVM浓度分别为20 mg/kg、40 mg/kg和60 mg/kg）对AVM的影响。在鸽脑中，DNA甲基化水平降低和DNMT mRNA表达下调呈剂量-时间依赖性。MBD 2作为一种去甲基化酶，其表达水平以剂量依赖性而非时间依赖性的方式显著增强。此外，与DNMT表达的变化相比，MBD 2的表达水平升高对基因组DNA低甲基化具有更强的影响。这些结果表明，AVM亚慢性剂量暴露可以影响整体DNA甲基化状态，并且这种机制与DNMTs和MBD 2表达水平的变化密切相关。(C)2014爱思唯尔爱尔兰有限公司版权所有。
As an effective insecticidal and nematicidal agent, avermectin (AVM) has been widely used in agricultural production and stock farming areas. Subsequently, the residues of AVM or its active metabolites in animal manure pose a toxic threat to non-target organisms in the environment. As the most characteristic epigenetic phenomena, DNA methylation status is a useful biological signal for the toxicity assessment of environmental chemical toxicants. In this study, analyses of the overall level of genomic DNA methylation were performed, and the expression levels of DNA methyltransferases (DNMTs), as well as demethylase methyl-CpG-binding domain protein 2 (MBD2), in pigeon brain tissues after subchronic exposure (with a AVM concentration of 20 mg/kg, 40 mg/kg and 60 mg/kg, respectively) to AVM for 30, 60 and 90 days were investigated. Global DNA hypomethylation and down-regulation of DNMT mRNA expression occurred in a dose-time-dependent manner in pigeon brains. The expression level of MBD2, which functions as a demethylase, was significantly enhanced in a dose-dependent but not time-dependent manner. In addition, the elevated expression level of MBD2 had a more robust effect on genomic DNA hypomethylation compared to changes in DNMT expression. Taken together, these results suggested that subchronic dose exposures of AVM could affect the global DNA methylation status, and this mechanism is closely related to changes in the expression levels of DNMTs and MBD2. (C) 2014 Elsevier Ireland Ltd. All rights reserved.