Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
J Toxicol Sci. 2024;49(6):281-288. doi: 10.2131/jts.49.281.
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)在信号转导中发挥生理作用,过量或慢性 NO 作为炎症介质具有毒性作用。NO 可逆地形成蛋白质 S-亚硝基化,并发挥与疾病进展相关的毒理学功能。DNA 甲基转移酶,与表观基因组相关的酶,其酶活性被 S-亚硝基化抑制。因此,过量或慢性 NO 暴露可能通过改变基因表达导致疾病。然而,慢性 NO 暴露对转录组的影响知之甚少。在这里,我们对 A549、AGS、HEK293T 和 SW48 细胞进行了转录组分析,这些细胞暴露于 100μM 的 NO 中 48 小时。结果表明,差异表达基因具有细胞特异性。基因本体分析表明,与细胞黏附或迁移相关的差异表达基因的功能特征在几种细胞系中上调。基因集富集分析表明,NO 刺激各种细胞系中炎症相关基因的表达。这一发现支持了先前的研究,表明 NO 与炎症性疾病密切相关。总的来说,本研究通过关注基因表达的变化,阐明了与 NO 相关的炎症性疾病的发病机制。