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转录组分析揭示氯化汞通过 caspase-3 非依赖性途径诱导人肺癌 H1299 细胞凋亡性细胞死亡。

Transcriptome Analysis Reveals HgCl Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

机构信息

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

出版信息

Int J Mol Sci. 2021 Feb 18;22(4):2006. doi: 10.3390/ijms22042006.

Abstract

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl treatment causes inhibition of cell growth via cell cycle arrest at G/G- and S-phase. In addition, HgCl induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl treatment. Altogether, these data show that HgCl induces apoptotic cell death through the dysfunction of mitochondria.

摘要

汞是环境中存在的一种有害有毒物质,以无机和有机两种形式存在。人类通过空气污染、食物或水的吸收以及个人护理产品接触无机汞,如氯化汞。本研究旨在研究 HgCl 对人非小细胞肺癌细胞 H1299 细胞活力、细胞周期、凋亡途径和转录组谱改变的影响。我们的数据表明,HgCl 通过在 G/G-和 S 期阻滞细胞周期导致细胞生长抑制。此外,HgCl 通过 caspase-3 非依赖性途径诱导细胞凋亡死亡。使用 RNA-seq 的综合转录组分析表明,HgCl 处理导致与细胞氮化合物代谢过程、细胞代谢和翻译相关的基因集的生物过程相关基因上调和下调。有趣的是,RNA-seq 的比较基因表达模式表明,低剂量 HgCl 处理显著改变了线粒体核糖体蛋白。总之,这些数据表明,HgCl 通过线粒体功能障碍诱导细胞凋亡死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bc/7922270/25a89d9c8a90/ijms-22-02006-g001.jpg

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