质谱学方法研究溴代阻燃剂与芳香烃受体蛋白的相互作用及介导毒性的蛋白质复合物

Brominated flame retardants (BFRs) are a group of emerging persistent organic pollutants (POPs), and are widely used in industrials and daily life. They have drawn an increasing attention due to their persistence, biological accumulation and being harmful to environment and human health. Previous study has suggested that aryl hydrocarbon receptor (AhR), a transcription factor, might mediate toxicological pathways of BFRs. However, the toxicological mechanism is still unclear. This project will establish advanced mass spectrometry (MS) methods of studying noncovalent protein complexes, including native electrospray mass spectrometry (Native ESI-MS), hydrogen deuterium exchange mass spectrometry (H/D Exchange MS), as well as the tandem affinity purification-liquid chromatography-tandem mass spectrometry (TAP-LC-MS/MS) techniques, to study the interactions of BFRs with AhR, screen and identify the proteins interacted with AhR in cell. In addition, mass spectrometry techniques combine with spectroscopy and molecular biology techniques to reveal the toxic mechanism of BFRs compounds. This project will provide experimental evidence and novel analytical methods to study the interactions of environmental pollutants with targeting proteins, and to reveal the toxicological mechanism of pollutants from molecular level which will provides theory basis for human health risk assessment.

溴代阻燃剂(BFRs)是一类新兴的持久性有机污染物(POPs)，广泛地应用于工业和日常生活中，因具有持久性、生物蓄积性并能对环境及人体健康产生危害而受到关注。前期研究显示BFRs可能通过信号转导因子芳香烃受体蛋白(AhR)介导其毒性，然而有关毒理机制尚不明确。本课题基于当今飞速发展的质谱技术，拟开发和建立研究非共价键蛋白复合物的先进质谱学(MS)方法，包括非变性电喷雾质谱（Native ESI-MS）、氢/氘交换质谱(H/D Exchange MS)以及串联亲和纯化-液相色谱-串联质谱联用（TAP-LC-MS/MS）等技术，从多个角度研究BFRs与AhR的相互作用，筛选和鉴定在细胞内与AhR相互作用的蛋白质复合物，结合细胞生物学方法阐释BFRs化合物诱导的细胞毒性机制。本项目将为系统地研究环境污染物与关键靶蛋白的相互作用，从分子水平上研究污染物的毒理机制和对健康的风险评估提供新的分析方法。

溴代阻燃剂(BFRs)是一类新兴的持久性有机污染物(POPs)，广泛地应用于工业和日常生活中，因具有持久性、生物蓄积性并能对环境及人体健康产生危害而受到关注。前期研究显示BFRs可能通过信号转导因子芳香烃受体蛋白(AhR)介导其毒性，然而有关毒理机制尚不明确。本课题基于当今飞速发展的质谱技术，拟开发和建立研究非共价键蛋白复合物的先进质谱学(MS)方法，包括非变性电喷雾质谱（Native ESI-MS）、氢/氘交换质谱(H/D Exchange MS)以及串联亲和纯化-液相色谱-串联质谱联用（TAP-LC-MS/MS）等技术，从多个角度研究BFRs与AhR的相互作用，筛选和鉴定在细胞内与AhR相互作用的蛋白质复合物，结合细胞生物学方法阐释BFRs化合物诱导的细胞毒性机制。本项目将为系统地研究环境污染物与关键靶蛋白的相互作用，从分子水平上研究污染物的毒理机制和对健康的风险评估提供新的分析方法。