Brownlee M, Vlassara H, Cerami A
Diabetes. 1983 Jul;32(7):680-4. doi: 10.2337/diab.32.7.680.
The effect of nonenzymatic glycosylation on the susceptibility of fibrin to degradation by the specific fibrinolytic enzyme plasmin was evaluated using both a fibrin plate assay and a fluorogenic synthetic plasmin substrate assay. Data from both types of experiments demonstrate that nonenzymatic glycosylation reduces the susceptibility of fibrin to plasmin degradation. Acetylation and carbamylation have qualitatively similar effects, indicating that chemical modification of lysine amino groups is the underlying phenomenon responsible for the observed degradative defect produced by glucose. Experimental conditions that increased the rate of nonenzymatic protein glycosylation (higher monosaccharide concentration, glucose-6-phosphate) were associated with correspondingly greater degrees of resistance to degradation by plasmin. Such reduced degradation of nonenzymatically glycosylated proteins in vivo may contribute to the accumulation of fibrin and several other proteins observed in those tissues most frequently affected by the complications of diabetes.
使用纤维蛋白平板测定法和荧光合成纤溶酶底物测定法,评估了非酶糖基化对纤维蛋白被特异性纤溶酶降解的敏感性的影响。两种类型实验的数据均表明,非酶糖基化降低了纤维蛋白对纤溶酶降解的敏感性。乙酰化和氨甲酰化具有定性相似的作用,表明赖氨酸氨基的化学修饰是导致葡萄糖产生所观察到的降解缺陷的潜在现象。增加非酶蛋白糖基化速率的实验条件(更高的单糖浓度、6-磷酸葡萄糖)与对纤溶酶降解的相应更大程度的抗性相关。体内非酶糖基化蛋白的这种降解减少可能导致在糖尿病并发症最常影响的那些组织中观察到的纤维蛋白和其他几种蛋白的积累。