Exploration of new biological marker of the health effects caused by environmental pollutants using genomic and proteomic analyses

利用基因组和蛋白质组分析探索环境污染物对健康影响的新生物标记

基本信息

批准号：
18590559
负责人：
ARISAWA Kokichi
金额：
$ 2.37万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

(1) Changes in gene expression of peripheral blood cells from women exposed to environmental cadmiumThe 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 cDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (mean age=68.7 years, Cd-exposed group) and 20 female residents in a non-Cd polluted area individually matched for age (control group).The mRNA levels of the Cd-exposed subjects were compared with those of respective controls. Median Cd concentrations in blood (3.55 μg/l) and urine (8.27 μg/g cr.)from the Cd-exposed group were 1.9-2.4 times higher than those of the control group. In cDNA microarray analysis, 137 up-regulated (>1.20-fold) and 80 down-regulated genes (<0.84-fold) were identified. Further, the authors chose 17 genes which were positively correlated with Cd concentrations in blood or urine, or which were involved in i … More mportant biological functions, and performed real-time PCR analysis. Significantly or marginally significantly increased expression was observed for CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4, CYP4F12, ITGAL and MT2, and significantly decreased expression was noted for BCL2A1 and COX7B. Increased expression of genes involved in protection against oxidative stress, apoptosis through the mitochondrial pathway and transporters were the characteristic features. Expression levels of SLC19A1 were positively correlated with Cd concentrations in blood and urine (r>0.5), suggesting that this was a candidate marker gene in low level exposure to environmental Cd.(2)Introduction of proteomic approach to environmental medicineRecent progress in life science technology and the availability of much information on genes obtained by genome analysis has enabled us to analyze the changes of proteins on a large scale. Sets of proteins are called proteomes, and proteomics is the scientific field of proteome analysis including differential, post translational modification and interaction analyses. Various proteomic techniques, particularly two-dimensional gel electrophoresis (2-DE), mass spectrometry, protein chip methods, and surface plasmon resonance (SPR), are very useful for acquiring proteomes in cells, tissues and body fluid, and for analyzing interactions between a protein and other biofactors including proteins. A proteomic approach is also useful for determining biomarkers of diseases and key proteins involved in various stages of metabolism such as differentiation, cell cycle and apoptosis. Environmental pollutants including endocrine disruptors inhibit activities of various organs in wild animals and humans. Proteomic approaches could be very useful tools for elucidating the mechanisms of damage caused by environmental pollutants. We reviewed the application of a proteomic approach to the field of environmental medicine. Less

（1）暴露于环境镉的女性外周血细胞的基因表达变化是本研究的目的是检查环境镉（CD）暴露对使用原始cDNA微阵列的外周血细胞基因表达谱的影响。研究人群由CD污染区域的20名女性居民组成（平均年龄= 68.7岁，CD暴露组）和20个非CD污染区域的女性居民单独匹配的年龄（对照组）。来自CD暴露组的血液（3.55μg/L）和尿液（8.27μg/g Cr。）中的CD浓度比对照组高的1.9-2.4倍。在cDNA微阵列分析中，确定了137个上调（> 1.20倍）和80个下调基因（<0.84倍）。此外，作者选择了17个基因，这些基因与血液或尿液中的CD浓度呈正相关，或者参与I…更重要的生物学功能，并进行了实时PCR分析。对于CASP9，TNFRSF1B，GPX3，HYOU1，SLC3A2，SLC19A1，SLC19A1，SLC35A4，CYP4F12，ITGAL和MT2，观察到了显着或略有显着增加的表达。涉及氧化应激，通过线粒体途径和转运蛋白的凋亡涉及的基因表达增加是特征。 Expression levels of SLC19A1 were positively correlated with Cd concentrations in blood and urine (r>0.5), suggesting that this was a candidate marker gene in low level exposure to environmental Cd.(2)Introduction of proteomic Approach to environmental medicine Recent progress in life science technology and the availability of much information on genes obtained by genome analysis has enabled us to analyze the changes of proteins on a large scale.蛋白质集称为蛋白质组，蛋白质组学是蛋白质组分析的科学领域，包括差异，翻译后修饰和相互作用分析。各种蛋白质组学技术，尤其是二维凝胶电泳（2-DE），质量蛋白质组学方法也有助于确定疾病的生物标志物和参与各种代谢阶段的关键蛋白质，例如分化，细胞周期和凋亡。包括内分泌干扰物在内的环境污染物会抑制各种器官在野生动物和人类中的活性。蛋白质组学方法可能是阐明环境污染物造成的损害机制的非常有用的工具。我们回顾了蛋白质组学方法在环境医学领域的应用。较少的