通过蛋白组转录组和基因筛选研究镉诱导生物毒性的机理

项目名称： 通过蛋白组转录组和基因筛选研究镉诱导生物毒性的机理

项目编号： No.31271272

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 施海峰

作者单位： 江苏大学

项目金额： 80万元

中文摘要： 镉是生物非必需有毒重金属元素，其能够通过必需元素如Fe，Ca，Zn和Mn的吸收系统进入机体，并在体内积累，能紧密结合含多个巯基的蛋白或化合物。镉自身不能催化产生自由基，然而镉通过多种途径间接产生活性氧（如中和还原性化合物谷胱甘肽、抑制SOD和过氧化氢酶活性、影响铁代谢增加游离态铁等）。镉结合蛋白能改变其活性，激活或抑制多种转录因子和细胞信号传导分子，改变细胞代谢途径，损伤细胞。诊断镉中毒的尿镉或尿中的标记蛋白在肾小管上皮细胞损伤后才出现。最近，我们发现镉能结合铁分子伴侣PCBP1并抑制其结合多聚胞嘧啶序列的活性。本项目拟用蛋白组学方法筛选检测早期镉中毒的生物标记蛋白，配合基因转录组方法确定镉在不同组织中引起毒性的主要途径；研究镉通过铁分子伴侣PCBP1影响细胞铁代谢的机制和途径；确定DMT-1和ZIP蛋白在肺组织细胞中吸收镉的作用；筛选能够减轻镉的细胞毒性的基因，并研究这些基因产物的功能。

中文关键词： 蛋白组；镉；基因芯片；自噬；胆固醇

英文摘要： Cadmium is a nonessential divalent heavy metal ion that causes toxicity in most organisms. The uptake of cd2+ is suggested to be mediated by the transporters and receptors for those essential metals such as Fe2+, Ca2+, Zn2+ or Mn2+. Cadmium tends to be accumulated in many organs and it binds to many bio-molecules particularly those with a lot of sulfhydryl groups which underlies the toxicity mechanism of cadmium. Although cd2+ is not a Fenton metal and therefore can not exert redox reactions in biological systems, it induces the formation of reactive oxygen species (ROS) indirectly by a number of ways such as depletion of redox scavengers GSH, inhibition of antioxidative enzymes and increase of labile iron pool. The association of cadmium with protein may modulate the biological function of that molecule and therefore activate or inhibit a variety of transcription factors also interfere the normal cellular signal transduction pathways. So cadmium can change the normal cellular metabolism pathway and cause cell damage. Cadmium is excreted from urine after the epithelial cells of the proximal tubule are damaged by the accumulated cadmium. The protein associated with such cell damage in urine is used as biomarker to diagnose cadmium nephrotoxicity. Recently, cd2+ was shown to interfere the function of an iron chape

英文关键词： proteomicas；cadmium；DNA microarray；autophage；cholesterol