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Downregulation of catalase by CuO nanoparticles via hypermethylation of CpG island II on the catalase promoter.
Toxicology Research ( IF 2.1 ) Pub Date : 2017-02-09 , DOI: 10.1039/c6tx00416d
Sandesh Chibber 1 , Amee Sangeet 1 , Shakeel Ahmed Ansari 2
Affiliation  

The advent of nanotechnology has led to new applications of copper as antibiotic treatment alternatives, nanocomposite coatings, catalysts, and lubricants among others. However, few studies address the impact of nano-size copper on the molecular mechanism of eukaryotic cells. Therefore, in the present study, the human hepatic cell line (WRL-68) was used to evaluate the molecular mechanism involved in the adverse effect of CuO NPs. CuO NPs were characterized by scanning electron microscopy and dynamic light scattering to confirm their 100 nm size and their purity was determined by Fourier transform infra-red spectroscopy. The side scattered intensity in WRL-68 cells at a CuO NP concentration of 250, 500, 750 and 1000 μM was found to be 108.83%, 126.86%, 189.03% and 250.88% respectively. The reactive oxygen species (ROS) generation at a CuO NP concentration of 1000 μM in WRL-68 cells was 417.75%. Moreover, the ROS induced methylation of CpG island II on the catalase promoter and downregulated catalase expression at the transcriptional level in WRL-68 cells. Furthermore, the activity of the catalase enzyme was found to decrease with an increase in concentration of CuO NPs. Subsequently, the proliferation of the WRL-68 cells was increased on exposure to the CuO NPs as demonstrated by the mitochondrial activity in the MTT assay. Conclusively, it is demonstrated that exposure of CuO NPs at 1000 μM for 24 h in the WRL-68 cell induced methylation of CpG island II via ROS on the catalase promoter and downregulated catalase expression at the transcriptional level. The obtained molecular mechanistic insights described adverse effects related to the CuO NPs.

中文翻译:

CuO纳米颗粒通过过氧化氢酶启动子上CpG岛II的甲基化使过氧化氢酶下调。

纳米技术的出现导致铜作为抗生素治疗替代品,纳米复合涂料,催化剂和润滑剂等的新应用。但是,很少有研究涉及纳米级铜对真核细胞分子机制的影响。因此,在本研究中,使用人肝细胞系(WRL-68)来评估涉及CuO NPs不良反应的分子机制。通过扫描电子显微镜和动态光散射对CuO NP进行表征,以确认其100 nm大小,并通过傅立叶变换红外光谱法确定其纯度。发现在250、500、750和1000μM的CuO NP浓度下WRL-68细胞的侧向散射强度分别为108.83%,126.86%,189.03%和250.88%。在WRL-68细胞中,CuO NP浓度为1000μM时,活性氧(ROS)产生为417.75%。此外,ROS在WRL-68细胞中在过氧化氢酶启动子上诱导CpG岛II甲基化,并在转录水平下调过氧化氢酶的表达。此外,发现过氧化氢酶的活性随CuO NPs浓度的增加而降低。随后,如MTT测定中的线粒体活性所证实的,WRL-68细胞的增殖在暴露于CuO NP时增加。结论是,证明了WRL-68细胞中1000μM的CuO NP暴露24 h通过过氧化氢酶启动子上的ROS诱导了CpG岛II的甲基化,并在转录水平下调了过氧化氢酶的表达。
更新日期:2017-02-09
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