Tohta Mizushima, Sho Kubota, Yuta Iijima, Nobumasa Takasugi, Takashi Uehara
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引用次数: 0
Abstract
Nitric oxide (NO) plays a physiological role in signal transduction and excess or chronic NO has toxic effects as an inflammatory mediator. NO reversibly forms protein S-nitrosylation and exerts toxicological functions related to disease progression. DNA methyltransferases, epigenome-related enzymes, are inhibited in enzymatic activity by S-nitrosylation. Therefore, excess or chronic NO exposure may cause disease by altering gene expression. However, the effects of chronic NO exposure on transcriptome are poorly understood. Here, we performed transcriptome analysis of A549, AGS, HEK293T, and SW48 cells exposed to NO (100 μM) for 48 hr. We showed that the differentially expressed genes were cell-specific. Gene ontology analysis showed that the functional signature of differentially expressed genes related to cell adhesion or migration was upregulated in several cell lines. Gene set enrichment analysis indicated that NO stimulated inflammation-related gene expression in various cell lines. This finding supports previous studies showing that NO is closely involved in inflammatory diseases. Overall, this study elucidates the pathogenesis of NO-associated inflammatory diseases by focusing on changes in gene expression.
一氧化氮(NO)在信号转导中发挥着生理作用,过量或慢性一氧化氮作为炎症介质具有毒性作用。一氧化氮可逆地形成蛋白质的 S-亚硝基化,并发挥与疾病进展有关的毒理学功能。DNA 甲基转移酶是与表观基因组有关的酶,S-亚硝基化会抑制其酶活性。因此,过量或长期暴露于 NO 可能会通过改变基因表达而致病。然而,人们对长期暴露于 NO 对转录组的影响知之甚少。在此,我们对暴露于 NO(100 μM)48 小时的 A549、AGS、HEK293T 和 SW48 细胞进行了转录组分析。结果表明,差异表达的基因具有细胞特异性。基因本体分析表明,与细胞粘附或迁移相关的差异表达基因的功能特征在多个细胞系中上调。基因组富集分析表明,NO 在不同细胞系中刺激了炎症相关基因的表达。这一发现支持了之前的研究,即 NO 与炎症性疾病密切相关。总之,这项研究通过关注基因表达的变化,阐明了 NO 相关炎症性疾病的发病机制。
期刊介绍:
The Journal of Toxicological Sciences (J. Toxicol. Sci.) is a scientific journal that publishes research about the mechanisms and significance of the toxicity of substances, such as drugs, food additives, food contaminants and environmental pollutants. Papers on the toxicities and effects of extracts and mixtures containing unidentified compounds cannot be accepted as a general rule.