TOM7在糖尿病大血管内皮损伤中的作用和机制研究

Endothelial cell damage is the initiative process of diabetic cardiovascular complications which is the most important factor relating to the death of diabetic patients. Translocase of the out membrane (Tom) which is the vital protein regulating the import of mitochondrial protein encoding by nuclear genome plays an important role in the regulation of mitochondrial function, oxidative damage and cell-aging. Tom7 which is one of the sub-units of Tom take a part in assembling of Tom sub-units and maintaining it stability. Our research-group has detected that Tom especially the Tom7 were reducing by the stimulation of high concentration of glucose (HG) when we researched in the relationship of HG and oxidative damage in vascular-endothelial cell. As the fold change of Tom7 is the most significantly one，we propose that Tom7 may be the key protein in the process of protectiing endothelial cell from damage induced by HG. In order to clarifying the function of Tom and Tom7 in vascular-endothelial cell damage induced by diabetes, in this project we plan to research in the following four parts including the relationship of Tom7 and glucose, the interaction of TOM7 and Bcl/Bax, the effect of NOX4 on TOM7 and the change of Tom7 and other sub-units of Tom under high concentration of glucose. These may provide new therapeutic targets and the points of penetration for the prevention and cure of diabetic vascular diseases.

糖尿病大血管并发症是糖尿病患者的首要致死原因，内皮细胞损伤是血管并发症的始动环节。线粒体外膜易位酶（Tom）是核基因编码的线粒体蛋白进入线粒体的关键蛋白，Tom在细胞的线粒体功能调节、氧化应激损伤、细胞衰老等过程发挥了重要作用。Tom7是Tom的亚基之一，主要负责Tom各亚基装配及结构稳定性调节。课题组在前期探究大血管内皮细胞中高糖与氧化损伤的关系的研究中发现，Tom亚基在高糖刺激的内皮细胞中显著下调，其中Tom7是表达差异最大的亚基，因此提出假设：上调Tom7水平可能对高糖导致的血管内皮损伤发挥保护作用。本项目计划通过探究Tom7和高糖导致的内皮损伤的关系、Tom7和凋亡相关Bcl-2/Bax蛋白的相互作用、NOX4对Tom7的影响以及Tom7与Tom其余亚基在高糖作用中的变化等四部分内容，以期阐明Tom7及Tom在糖尿病血管病变中的作用，为糖尿病大血管病变的防治研究提供新的靶点。