Ozdemir Aylin M, Hopfer Ulrich, Rosca Mariana V, Fan Xing-Jun, Monnier Vincent M, Weiss Miriam F
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Am J Nephrol. 2008;28(1):14-24. doi: 10.1159/000108757. Epub 2007 Sep 20.
The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells.
A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs. Therefore in diabetes, plasma proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs.
The model system was electrically resistant polarized renal proximal tubular epithelial cells in monolayer culture. The model proteins comprise a well-characterized AGE, methylglyoxal-modified bovine serum albumin (MGO-BSA), and unmodified BSA.
Renal proximal tubular cells handle MGO-BSA and native BSA in markedly disparate ways, including differences in: (1) kinetics of binding, uptake, and intracellular accumulation, (2) processing and fragmentation, and (3) patterns of electrical conductance paralleling temporal changes in binding, uptake and processing.
These differences support the idea that abnormal protein processing by the renal tubule can be caused by abnormal proteins, thereby forging a conceptual link between the pathogenic role of AGEs and early changes in tubular function that can lead to hypertrophy and nephropathy in diabetes.
本研究旨在了解晚期糖基化终产物（AGE）修饰蛋白对肾近端小管细胞的细胞效应。
近端小管的主要功能是重吸收和处理滤过的蛋白质。糖尿病的特征是组织和循环中被AGE修饰的蛋白质数量增加。因此，在糖尿病中，肾小球滤过并呈现给肾近端小管的血浆蛋白很可能被AGE高度修饰。
模型系统为单层培养的具有电阻性的极化肾近端小管上皮细胞。模型蛋白包括一种特征明确的AGE，即甲基乙二醛修饰的牛血清白蛋白（MGO-BSA），以及未修饰的BSA。
肾近端小管细胞处理MGO-BSA和天然BSA的方式明显不同，包括：（1）结合、摄取和细胞内积累的动力学；（2）加工和片段化；（3）与结合、摄取和加工的时间变化平行的电导模式。
这些差异支持这样一种观点，即肾小管异常的蛋白质加工可能由异常蛋白质引起，从而在AGE的致病作用与可导致糖尿病中肾小管肥大和肾病的早期功能变化之间建立了概念上的联系。
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