金属离子对细胞紧密连接的作用、机制和研究新方法

项目名称： 金属离子对细胞紧密连接的作用、机制和研究新方法

项目编号： No.21271012

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 杨晓达

作者单位： 北京大学

项目金额： 80万元

中文摘要： 生物屏障是生物体控制物质转运的重要手段。在生物屏障结构中，细胞之间的紧密连接（Tight junction, TJ) 是其完整性的结构基础之一。TJ的功能失常与某些疾病和金属毒性都有重要关联；特别是抗糖尿病钒化合物与TJ的作用可能与其肾毒性密切相关。本项目计划应用稀土配合物和胶体金等为探针，建立TJ开放程度和模式分析的新方法，进而研究钒、铅、汞、锌等金属离子及化合物对TJ开放的调节作用，并通过分析金属离子对紧密连接蛋白的表达、蛋白磷酸化修饰以及对细胞相关信号转导过程的作用，探索和阐明金属离子对TJ调节作用的化学和分子机制，从而推进金属化合物毒性的化学基础研究，为发现新的抗糖尿病钒化合物和扩展稀土配合物/无机纳米材料在医学检验中的应用提供新的科学依据。

中文关键词： 紧密连接；钒；锌；纳米原子簇；荧光探针

英文摘要： Biological barriers are essential for controlling flux and transport of substances. The tight junction (TJ) is of crucial importance in the structural integrity of biological barriers. Alternations in structures and functions of tight junction are associated with some diseases and metal toxicity; particularly, the renal toxicity of anti-diabetic vanadium compounds could be closely associated with vanadium-induced tight junction damages.The aim of this project is to study the actions and mechanisms of vanadium, lead, mercury, zinc and other metal compounds on the structures and functions of tight junction while developing novel methods to determine the permeability and modes of tight junction opening by use of lanthanide complexes and gold nanoparticles as series of probes. In addition, the project will analyze the effects of metal compounds on expression of tight junction proteins and their phosphorylation modification as well as major signal transduction pathways related, thus elucidating the molecular mechanisms of regulating tight junction by metal compounds. Our results will provide new insight into the chemical bases of metal toxicity and help to discover safer anti-diabetic vanadium agents and novel diagnostic probes using lanthanide complexes and inorganic nano materials.

英文关键词： tight junction；vanadium；zinc；nanocluster；fluorescent probe