Role of epigenetic mechanisms in diabetic vascular complications

糖尿病并发症，包括心脏病发作、中风、肾脏疾病和失明，似乎与高血糖(糖)水平有关，但葡萄糖本身如何导致终末器官损伤仍有待完全确定。在这项提议中，有人认为葡萄糖的长期损害作用与其通过直接影响DNA及其被称为组蛋白的覆盖而破坏基因调控的能力有关。具体地说，葡萄糖可能通过改变某些称为氧化途径的生化途径来干扰酶，这些酶影响DNA和相关分子的结构，导致许多蛋白质表达的改变。其中一种被称为核因子kappa B的蛋白质在糖尿病中被激活，可能是通过调节这些酶的机制来激活的，这些酶在改变基因结构方面发挥着核心作用。通过在分子水平上阐明葡萄糖对基因和蛋白质的影响的确切机制，将有可能针对这些分子并开发新的治疗方法来预防、延缓或逆转糖尿病常见的血管并发症。

Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called oxidation pathways, interferes with enzymes which affect the structure of DNA and related molecules resulting in altered expression of many proteins. One of these proteins known as NF kappa B is activated in diabetes, probably by mechanisms involving regulation of these enzymes which play a central role in modifying gene structure. By clarifying the exact mechanisms at a molecular level that mediate the effect of glucose on genes and proteins it will be possible to target these molecules and develop new treatments to prevent, retard or reverse the blood vessel complications that are so common in diabetes.