Gilcrease M Z, Hoover R L
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232.
Am J Pathol. 1991 Nov;139(5):1089-97.
Increased nonenzymatic glycation of proteins has been implicated in the pathogenesis of diabetic vascular disease. The authors have shown by 3H-NaBH4 reduction of nonenzymatic glycation adducts that endothelial cell membrane proteins undergo increased nonenzymatic glycation in vitro when exposed to elevated concentrations of glucose. Increased nonenzymatic glycation also was found in vivo for microvascular endothelial cells isolated from streptozotocin-induced diabetic rats compared with control rats. Cultured monocytes have previously been reported to express receptors for certain nonenzymatic glycation adducts. The authors have further investigated whether monocyte interactions with endothelium are altered by the presence of nonenzymatic glycation adducts on endothelium. Adherence assays were performed in the presence of elevated concentrations of glucose with decreased NaCl levels to maintain normal osmolarity (as occurs physiologically). Although monocyte adherence to endothelium and levels of early nonenzymatic glycation adducts increased under these conditions, the increased adherence appears to be due to the altered NaCl levels. In fact, freshly isolated monocytes (in contrast to what has been found for macrophages and activated monocytes) were shown not to express appreciable numbers of receptors for nonenzymatic glycation adducts.
蛋白质非酶糖基化增加与糖尿病血管疾病的发病机制有关。作者通过用³H-NaBH₄还原非酶糖基化加合物表明,当暴露于高浓度葡萄糖时,内皮细胞膜蛋白在体外会发生非酶糖基化增加。与对照大鼠相比,从链脲佐菌素诱导的糖尿病大鼠分离的微血管内皮细胞在体内也发现非酶糖基化增加。此前有报道称培养的单核细胞表达某些非酶糖基化加合物的受体。作者进一步研究了内皮细胞上存在非酶糖基化加合物是否会改变单核细胞与内皮细胞的相互作用。在高浓度葡萄糖存在且氯化钠水平降低以维持正常渗透压(如生理状态下)的情况下进行黏附试验。尽管在这些条件下单核细胞与内皮细胞的黏附以及早期非酶糖基化加合物水平增加,但黏附增加似乎是由于氯化钠水平改变所致。事实上,新鲜分离的单核细胞(与巨噬细胞和活化单核细胞的情况相反)显示不表达大量非酶糖基化加合物的受体。