铅暴露引起的U251细胞基因表达差异及其分析  

Analysis of differential expression genes in glioma U251 cell exposed to lead and gene ontology

作　　者：孟金萍[1] 孙淑华[1] 王艳蓉[1] 杨旭[1] 刘云波[1] 

机构地区：[1]中国医学科学院北京协和医学院实验动物研究所,北京100021

出　　处：《毒理学杂志》2010年第3期193-198,共6页Journal of Toxicology

基　　金：国家973项目（2002CB512901）

摘　　要：目的铅暴露体外培养的人神经胶质瘤U251细胞,分析基因表达改变和分析差异基因功能,探讨铅暴露与疾病的相关性。方法使用乙酸铅(终浓度为400μg/ml)分别暴露U251细胞8h和24h,提取RNA,通过人全基因组芯片进行基因表达谱分析,芯片扫描结果经归一化处理,设定Ratio值<0.5或≥2为表达有差异基因。对这些基因进行基因本体(Gene Ontology,GO)分类,查询差异基因与不同疾病的相关性。结果铅暴露U251细胞导致2840条基因差异表达,GO分类显示这些基因参与的生物过程主要有依赖DNA的转录调控、细胞粘附、磷酸化以及细胞间的信息传递等;参与细胞膜构成,在细胞中的定位主要是线粒体和细胞外。这些基因与疾病密切相关,主要的疾病有白血病(leukemia)、动脉硬化(atherosclerosis)、阿兹海默症(Alzheimer's disease)、糖尿病(diabetes mellitus)、精神分裂症(schizophrenia)、以及慢性炎症和癌变等。结论铅暴露导致大量基因表达改变,致使细胞功能失常,并可能诱发多种疾病。Objective To investigate the change of gene expression in hunman neurogliomal U251 cells that exposed to lead,to analyze the relativity of lead exposure with differential diseases. Methods The Human neurogliomal U251 cells were exposed to lead with LD50 concentration for 8h and 24h,then the total RNA were extracted. Microarray technique was used to screen out differentially expressed genes to analyze the effect of lead in human neurogliomal U251 cells. We defined the gene as differential expression with ratio value 0. 5 or ≥2. The differentially expressed genes were classified by using the Ontology taxonomy. The differentially expressed gene related disease was searched in MAS database. Results Compared with the control group,2840 genes showed distinct differential expression after lead exposure. Interrelated disease such as leukemia, atherosclerosis,Alzheimer’s disease,diabetes mellitus,schizophrenia and chronic inflammation. Conclution Lead exposure resulted in the alteration of gene expression for a large number of genes in the U251 cells,and led to the abnormality of cell function,which have the potential to cause many diseases.

关 键 词：铅 基因芯片 GO分类 

分 类 号：R114[医药卫生—卫生毒理学]