Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium
Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium
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DOI：
10.1016/j.tox.2008.12.004
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发表时间：
2009-03-04
期刊：
影响因子：
4.5
通讯作者：
Arisawa, Kokichi
中科院分区：
文献类型：
--
作者：
Dakeshita, Satoru;Kawai, Tomoko;Arisawa, Kokichi
本研究的目的是研究环境镉（Cd）暴露对外周血细胞基因表达谱的影响，使用原始寡核苷酸微阵列。研究人群包括20名cd污染地区的女性居民（cd暴露组）和20名年龄匹配的非cd污染地区的女性居民（对照组）。使用含有1867个基因的寡odna探针的微阵列，比较cd暴露受试者的mRNA水平。Cd暴露组的血液中Cd浓度（3.55 μ g/l）和尿液中Cd浓度（8.25 μ g/g肌酐）分别比对照组高2.4倍和1.9倍。微阵列分析显示，与对照组相比，cd暴露组显著上调137个基因，下调80个基因。匠心途径分析应用程序（IPA）显示，差异表达的基因可能改变氧化应激和线粒体依赖的凋亡途径。在差异表达基因中，5个基因的表达与血或尿中Cd浓度呈正相关。实时荧光定量PCR （RT-PCR）分析证实CASP9、TNFRSF1B、GPX3、HYOU1、SLC3A2、SLC19A1、SLC35A4和ITGAL基因显著上调，BCL2A1和COX7B基因显著下调。在调整了两组背景特征的差异后，我们最终确定了7个cd响应基因（CASP9、TNFRSF1B、GPX3、SLC3A2、ITGAL、BCL2A1和COX7B），它们都构成了一个通过IPA控制氧化应激反应的网络。这7个基因可能是对慢性低水平接触镉的健康风险评估有用的标记基因。(C) 2008爱思唯尔爱尔兰有限公司。版权所有。
The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes. Median Cd concentrations in blood (3.55 mu g/l) and urine (8.25 mu g/g creatinine) from the Cd-exposed group were 2.4- and 1.9-times higher than those of the control group, respectively. Microarray analysis revealed that the Cd-exposed group significantly up-regulated 137 genes and down-regulated 80 genes, compared with the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that differentially expressed genes were likely to modify oxidative stress and mitochondria-dependent apoptosis pathways. Among differentially expressed genes, the expression of five genes was positively correlated with Cd concentrations in blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for differences in the background characteristics of the two groups, we finally identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL, BCL2A1, and COX7B), all of which constituted a network that controls oxidative stress response by IPA. These seven genes may be marker genes useful for the health risk assessment of chronic low level exposure to Cd. (C) 2008 Elsevier Ireland Ltd. All rights reserved.