Rellier N, Ruggiero D, Lecomte M, Lagarde M, Wiernsperger N
Diabetic Microangiopathy Research Unit, LIPHA-INSERM U352, INSA-Lyon, Villeurbanne, France.
Biochem Biophys Res Commun. 1997 Jun 18;235(2):281-5. doi: 10.1006/bbrc.1997.6768.
In order to investigate the mechanisms involved in diabetic retinopathy, we studied the effects of advanced glycosylation end products (AGE) on retinal microvascular cell glycoproteins. Bovine retinal pericytes (BRP) and endothelial cells (BREC) were incubated in the presence of AGE-modified albumin and cell glycoproteins analyzed by lectin affinoblotting and metabolic radiolabeling with sugar precursors. Selective modifications in the glycoprotein sugar chains were observed mainly in BREC and for a 210 kDa membrane glycoprotein. Indeed, a 40% decrease of alpha(2,3) sialic acid, beta(1,3) galactose or alpha(1,6) fucose content was observed without significant protein amount changes. These glycoprotein alterations were related to the concentration of AGE. Neither BRP nor BREC glycoproteins were modified when cells were incubated with high glucose or fructose concentrations. These results suggest a new diabetic pathogenic mechanism in which a protein post-translational modification, in this case glycation, could modify another post-translational process such as the enzymatic glycosylation.
为了研究糖尿病视网膜病变的发病机制，我们研究了晚期糖基化终产物（AGE）对视网膜微血管细胞糖蛋白的影响。将牛视网膜周细胞（BRP）和内皮细胞（BREC）在AGE修饰的白蛋白存在下孵育，并用凝集素亲和印迹法和糖前体的代谢放射性标记法分析细胞糖蛋白。糖蛋白糖链的选择性修饰主要在BREC中观察到，并且针对一种210 kDa的膜糖蛋白。实际上，观察到α（2,3）唾液酸、β（1,3）半乳糖或α（1,6）岩藻糖含量降低了40%，而蛋白质含量没有显著变化。这些糖蛋白改变与AGE的浓度有关。当细胞与高浓度葡萄糖或果糖孵育时，BRP和BREC糖蛋白均未被修饰。这些结果提示了一种新的糖尿病致病机制，即蛋白质翻译后修饰（在这种情况下为糖基化）可能会改变另一种翻译后过程，如酶促糖基化。
