Vlassara H
Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Ann Med. 1996 Oct;28(5):419-26. doi: 10.3109/07853899608999102.
The late rearrangements of the covalent nonenzymatic modification of proteins by glucose, called advanced glycation end-products (AGEs), have been shown to accumulate in diabetic and ageing tissues. AGEs elicit a wide range of cell-mediated responses leading to vascular dysfunction, matrix expansion and athero- and glomerulosclerosis. Cellular responses are thought to be largely induced through an AGE-specific cell-surface receptor complex (AGEr). Interaction of AGE-modified proteins with these cells may serve diverse purposes, including disposal of senescent AGE-modified molecules and initiation of tissue repair and protein turnover. In humans, the normal renal clearance rate for the AGE-degradation products found in serum, AGE peptides (AGEp), correlates inversely with renal creatinine clearance rate. Of note, circulating AGEp include reactive intermediates which readily attach covalently to either insoluble matrix collagen or serum proteins, e.g. low-density lipoproteins (LDL), to form AGEp collagen and AGEp-LDL. Consistent with this, diabetic and nondiabetic patients with renal failure (a group highly susceptible to accelerated atherosclerosis) exhibit markedly elevated AGE-modified serum LDL. In summary, in addition to glucose-derived AGEs, the endogenously produced degradation products, AGE peptides, can amplify tissue damage and thus account as distinct toxins. The effects may particularly accelerate glucose toxicity in certain individuals that are genetically susceptible to diabetic renal and extrarenal disease.
葡萄糖对蛋白质进行的共价非酶修饰的晚期重排产物，即所谓的晚期糖基化终产物（AGEs），已被证明会在糖尿病和衰老组织中积累。AGEs引发多种细胞介导的反应，导致血管功能障碍、基质扩张以及动脉粥样硬化和肾小球硬化。细胞反应被认为主要是通过一种AGE特异性细胞表面受体复合物（AGEr）诱导的。AGE修饰的蛋白质与这些细胞的相互作用可能有多种目的，包括清除衰老的AGE修饰分子以及启动组织修复和蛋白质更新。在人类中，血清中发现的AGE降解产物AGE肽（AGEp）的正常肾脏清除率与肾脏肌酐清除率呈负相关。值得注意的是，循环中的AGEp包括反应性中间体，它们很容易与不溶性基质胶原蛋白或血清蛋白（如低密度脂蛋白（LDL））共价结合，形成AGEp胶原蛋白和AGEp-LDL。与此一致的是，患有肾衰竭的糖尿病和非糖尿病患者（这是一组极易发生加速动脉粥样硬化的人群）的AGE修饰血清LDL明显升高。总之，除了葡萄糖衍生的AGEs外，内源性产生的降解产物AGE肽可加剧组织损伤，因此可被视为独特的毒素。这些影响可能会特别加速某些对糖尿病肾病和肾外疾病具有遗传易感性的个体的葡萄糖毒性。
