Characterisation of Novel AGE Binding Proteins: Implications for Diabetic Vascular Complications.

该项目将探索一个被称为晚期糖基化的过程，特别是它如何导致糖尿病的器官损伤。糖尿病的特点是血糖水平持续升高，血糖水平与蛋白质相互作用产生称为晚期糖基化终产物（AGEs）的产物。这些AGEs与其他蛋白质结合，其中一些已经被分离出来，被认为是受体。我们自己的研究小组已经确定了一个新的蛋白质家族，称为ERM蛋白质，它与AGEs结合。这是一个非常新颖的发现，现在需要进行更详细的研究。ERM蛋白包括ezrin、radixin和moiesin，它们存在于糖尿病并发症的许多部位，包括肾脏、视网膜和血管壁。它们具有多种功能，包括对细胞粘附和细胞结构的影响。这在糖尿病中很重要，因为已经观察到细胞的变化，包括结构的改变。这项资助将在分子和细胞水平上描述AGEs和ERM蛋白之间的相互作用。它将定义AGEs如何通过与ERM蛋白的相互作用影响细胞。这些研究有可能导致调节AGE-ERM相互作用的治疗方法，从而延缓或预防糖尿病血管并发症。这些并发症是糖尿病患者发病和死亡的主要原因，具有重要的临床意义。此外，糖尿病是我们社区过早动脉粥样硬化的主要原因，糖尿病肾病是西方世界终末期肾衰竭的主要原因，糖尿病视网膜病变（眼病）是工作年龄人口失明的主要原因。

This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.