Stolzing Alexandra, Widmer Rebecca, Jung Tobias, Voss Peter, Grune Tilman
Kroto Research Institute and Centre for Nanoscience and Technology, North Campus, Sheffield University, Sheffield, UK.
Free Radic Biol Med. 2006 Mar 15;40(6):1017-27. doi: 10.1016/j.freeradbiomed.2005.10.061. Epub 2005 Nov 17.
Glycated protein products are formed upon binding of sugars to lysine and arginine residues and have been shown to accumulate during aging and in pathologies such as Alzheimer disease and diabetes. Often these glycated proteins are transformed into advanced glycation end products (AGEs) by a series of intramolecular rearrangements. In the study presented here we tested the ability of microglial cells to degrade BSA-AGE formed by glycation reactions of bovine serum albumin (BSA) with glucose and fructose. Microglial cells are able to degrade BSA-AGEs to a certain degree by proteasomal and lysosomal pathways. However, the proteasome and lysosomal proteases are severely inhibited by cross-linked BSA-AGEs. BSA-AGEs are furthermore able to activate microglial cells. This activation is accompanied by an enhanced degradation of BSA-AGE. Therefore, we conclude that microglial cells are able to degrade glycated proteins, although cross-linked protein-AGEs have an inhibitory effect on proteolytic systems in microglial cells.
糖基化蛋白产物是在糖类与赖氨酸和精氨酸残基结合时形成的，并且已证实在衰老过程以及诸如阿尔茨海默病和糖尿病等病理状态下会积累。通常，这些糖基化蛋白会通过一系列分子内重排转化为晚期糖基化终产物（AGEs）。在本文所呈现的研究中，我们测试了小胶质细胞降解由牛血清白蛋白（BSA）与葡萄糖和果糖发生糖基化反应形成的BSA-AGE的能力。小胶质细胞能够通过蛋白酶体和溶酶体途径在一定程度上降解BSA-AGE。然而，蛋白酶体和溶酶体蛋白酶会受到交联的BSA-AGE的严重抑制。此外，BSA-AGE能够激活小胶质细胞。这种激活伴随着BSA-AGE降解的增强。因此，我们得出结论，小胶质细胞能够降解糖基化蛋白，尽管交联的蛋白-AGE对小胶质细胞中的蛋白水解系统具有抑制作用。
