Waczulíkova I, Sikurová L, Cársky J, Strbová L, Krahulec B
Department of Biophysics and Chemical Physics, Faculty of Mathematics, Physics, and Information, Comenius University, Bratislava, Slovakia.
Gen Physiol Biophys. 2000 Dec;19(4):381-92.
Changes in the physico-chemical properties of erythrocyte membranes induced by nonenzymatic glycation as well as the possible prevention of their rise were studied. Using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), fluorescence anisotropy values were determined in erythrocyte membranes isolated from type 1 and type 2 diabetic patients with and without complications. The mean anisotropy values for the groups of diabetic patients were significantly higher than those for the control group (p < 0.01). This indicated pathologically decreased fluidity in cell membranes in the diabetics regardless of the type of diabetes or the presence of complications. The fluorescence anisotropy positively correlated (p < 0.01) with clinical parameters, such as glycohaemoglobin and plasma cholesterol content, which are important for the monitoring of the compensation status of the diabetic patient. Our results support the suggestion that protein crosslinking and oxidative stress induced by nonenzymatic glycation contribute to changes in the physico-chemical properties of erythrocyte membranes. In vitro testing of a new potential drug resorcylidene aminoguanidine (RAG) showed its ability to increase significantly (p < 0.001), to various extent (p < 0.01), the fluidity of both diabetic and control erythrocyte membranes. Upon the administration of RAG, reduced fluorescence anisotropy values for the groups of diabetic patients approached the normal values obtained for the controls. This may play an important role in the improvement of impaired cell functions found in diabetes that are controlled by the cell membrane.
研究了非酶糖基化诱导的红细胞膜物理化学性质的变化以及可能防止其升高的方法。使用荧光探针1,6-二苯基-1,3,5-己三烯(DPH),测定了从有或无并发症的1型和2型糖尿病患者分离的红细胞膜中的荧光各向异性值。糖尿病患者组的平均各向异性值显著高于对照组(p<0.01)。这表明无论糖尿病类型或是否存在并发症,糖尿病患者细胞膜的流动性均呈病理性降低。荧光各向异性与临床参数如糖化血红蛋白和血浆胆固醇含量呈正相关(p<0.01),这些参数对于监测糖尿病患者的代偿状态很重要。我们的结果支持以下观点:非酶糖基化诱导的蛋白质交联和氧化应激导致红细胞膜物理化学性质的变化。对一种新的潜在药物间苯二亚甲基氨基胍(RAG)的体外测试表明,它能够显著提高(p<0.001)糖尿病和对照红细胞膜的流动性,且在不同程度上(p<0.01)均可提高。给予RAG后,糖尿病患者组降低的荧光各向异性值接近对照组的正常水平。这可能在改善糖尿病中由细胞膜控制的受损细胞功能方面发挥重要作用。