Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells
Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells
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DOI：
10.1016/j.tiv.2014.02.004
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Kim, Yong-Sik
中科院分区：
文献类型：
--
作者：
Jung, Ha-Na;Zerin, Tamanna;Kim, Yong-Sik
在韩国，与加湿器消毒剂使用相关的儿童和孕妇肺部疾病已成为一个主要问题。常见的消毒剂是聚胍（PHMG），其是胍类防腐剂的成员。本研究旨在阐明PHMG的细胞毒性作用及其对人肺泡上皮细胞A549基因表达的影响。细胞活力分析显示PHMG的有效细胞毒性，在低至5 μ g/mL时细胞死亡明显。死亡是剂量和时间依赖性的，并与细胞内活性氧的形成，和细胞凋亡显着，即使在2 μ g/mL的浓度。使用DNA微阵列分析研究了暴露于5 μ g/mL PHMG 24小时后A549细胞中的基因表达谱。与细胞死亡进展相关的基因表达变化包括诱导与凋亡、自噬、纤维化和细胞周期相关的基因。然而，编码抗氧化和解毒酶的基因的表达下调或不受影响。通过定量逆转录-聚合酶链反应和Western印迹分析证实了所选基因表达的改变。集体数据表明，PHMG通过产生细胞内活性氧和改变基因表达来赋予细胞毒性。(C)2014爱思唯尔有限公司版权所有。
In Korea, lung disease of children and pregnant women associated with humidifier disinfectant use has become a major concern. A common sterilizer is polyhexamethylene guanidine (PHMG), a member of the guanidine family of antiseptics. This study was done to elucidate the putative cytotoxic effect of PHMG and the PHMG-mediated altered gene expression in human alveolar epithelial A549 cells in vitro. Cell viability analyses revealed the potent cytotoxicity of PHMG, with cell death evident at as low as 5 mu g/mL. Death was dose- and time-dependent, and was associated with formation of intracellular reactive oxygen species, and apoptosis significantly, at even 2 mu g/mL concentration. The gene expression profile in A549 cells following 24 h exposure to 5 mu g/mL of PHMG was investigated using DNA microarray analysis. Changes in gene expression relevant to the progression of cell death included induction of genes related to apoptosis, autophagy, fibrosis, and cell cycle. However, the expressions of genes encoding antioxidant and detoxifying enzymes were down-regulated or not affected. The altered expression of selected genes was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses. The collective data suggest that PHMG confers cellular toxicity through the generation of intracellular reactive oxygen species and alteration of gene expression. (C) 2014 Elsevier Ltd. All rights reserved.