项目名称: 二维色谱—质谱技术在金属化合物诱导蛋白表达差异研究中的应用
项目编号: No.21277151
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 环境科学、安全科学
项目作者: 何滨
作者单位: 中国科学院生态环境研究中心
项目金额: 82万元
中文摘要: 部分金属是生物体必需元素,生物体内这些元素的缺失或富集均可导致生物毒性,有毒金属污染物也会导致某些金属蛋白和其他蛋白的表达差异,对生物和人体健康产生严重的威胁。单纯的总量测定和小分子有机金属化合物的形态分析难以解释有毒金属等污染物在生物体中的富集现象和致毒机理,而生物体经金属污染物暴露后的蛋白差异表达和金属结合蛋白的分离、鉴定将有利于揭示这些问题的本质。本项目将针对环境中有毒金属污染物开展以细胞及生物体为模型的暴露实验,建立2D-LC、2-DE与ICP-MS、MALDI-TOF-MS和ESI-MS联用的分析测试系统,对细胞及生物体相关靶器官内金属蛋白的分离和鉴定、生物体内蛋白的表达差异以及金属等污染物在生物体内的吸收、迁移转化、代谢途径、与生物大分子的相互作用等进行研究,从而从分子水平,特别是蛋白质水平揭示外源性有毒金属化合物对生物体生理功能的影响和致毒机理。
中文关键词: 金属;蛋白质;相互作用;联用系统;致毒机理
英文摘要: Some metals are essential for organisms. Deficiency or excess of these metals results biotoxicity. Exposure to toxical heavy metals can induce and repress the expression of some metal-containing or other related proteins, which cause negative effects to human health. Information of quantification of total concentration of metals and speciation of organometals is insufficient to explain the mechanism of enrichment and toxication in organisms. Study on differential expression of proteins after exposure to toxic metals and identification of differentially expressed proteins are useful for solving the problems. In this project we will establish several hyphenated systems including two dimensional liquid chromatography and two dimensional electrophoresis with ICP-MS and MALDI-ESI-MS. After exposing to toxic metals we will separate, quantitate and identify metal-contain proteins in model animals and cells, find out the different protein expression signatures for each pollutant and explore the absorption, transportation,pathway of metabolism of toxic metals as well as the interaction between metals and biomacromolecules in order to reveal the influence and toxic mechanisms of exogenous toxic heavy metals from molecular especially protein levels.
英文关键词: metal;protein;interaction;hyphenated systems;toxic mechanism