Yamada Hirotomo, Koizumi Shinji
Division of Health Effects Research, National Institute of Industrial Health, Kawasaki, Japan.
Ind Health. 2002 Apr;40(2):159-66. doi: 10.2486/indhealth.40.159.
Cadmium (Cd) is a hazardous heavy metal present in working and living environments. Cd affects many cellular functions, but little is known about the mechanisms of its toxicity and cellular defense against it. Recently, advanced gene expression analysis employing DNA microarrays provided us the means to profile the expression of thousands of genes simultaneously. We describe here a study of Cd-induced gene expression profile. Messenger RNA was prepared from HeLa cells exposed to a non-lethal dose of CdSO4, and analyzed by the use of an array consisting of 7,075 human cDNAs. Many stress response genes including those coding for metallothioneins and heat shock proteins were observed to be induced by Cd. The cellular metabolism inclined toward the synthesis of cysteine and glutathione after Cd exposure. Anti-oxidant genes also appeared to be induced to protect cell components and to quench reactive oxygen species. Ubiquitin pathway was activated as well probably to degrade proteins which might not be renatured. These data suggest that human cells mobilize every genomic resource (induction of some genes and repression of others) to overcome cytotoxicity caused by Cd.
镉(Cd)是一种存在于工作和生活环境中的有害重金属。镉会影响许多细胞功能,但对其毒性机制以及细胞对其的防御机制却知之甚少。最近,采用DNA微阵列的先进基因表达分析为我们提供了同时分析数千个基因表达情况的方法。我们在此描述一项关于镉诱导基因表达谱的研究。从暴露于非致死剂量硫酸镉的HeLa细胞中制备信使核糖核酸(mRNA),并使用由7075个人类互补DNA(cDNA)组成的阵列进行分析。观察到许多应激反应基因,包括那些编码金属硫蛋白和热休克蛋白的基因,会被镉诱导。镉暴露后,细胞代谢倾向于半胱氨酸和谷胱甘肽的合成。抗氧化基因似乎也被诱导,以保护细胞成分并清除活性氧。泛素途径也可能被激活,以降解可能无法复性的蛋白质。这些数据表明,人类细胞会调动所有基因组资源(一些基因的诱导和其他基因的抑制)来克服由镉引起的细胞毒性。