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首页> 外文期刊>International Journal of Environmental Research and Public Health >Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays
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Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

机译：低剂量砷暴露于人和培养的心肌细胞中的基因表达改变：实时PCR阵列的评估。

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Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-mM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.
机译：慢性砷暴露导致皮肤，肺癌和膀胱癌以及心血管疾病和糖尿病的风险更高。这项研究的目的是使用新型RT-PCR TaqMan低密度阵列（TLDA），研究159名长期接触饮用水中砷的人对血液淋巴细胞中所选基因表达的影响。我们发现，肿瘤坏死因子-α（TNF-α）的表达可激活炎症和NF-κB依赖的生存途径，与水和尿中砷的含量密切相关。编码钾离子通道蛋白的KCNA5的表达与水和脚趾甲砷水平呈正相关。 2和11个基因的表达分别与指甲和尿砷呈正相关。由于据报道砷暴露与人类长时间QT间隔和血管疾病有关，因此我们也使用此TLDA分析体外暴露于砷的人类心肌细胞中的基因表达。离子通道基因CACNA1，KCNH2，KCNQ1和KCNE1的表达被1-mM砷下调。某些常见途径的改变，包括与氧化应激，炎症信号传导和离子通道功能有关的途径，可能掩盖了与砷有关的疾病，如癌症，心血管疾病和糖尿病，看似完全不同。

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