Degradation of oxidized extracellular proteins by microglia

Degradation of oxidized extracellular proteins by microglia
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DOI:
10.1016/s0003-9861(02)00003-6
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发表时间:
2002-04-15
影响因子:
3.9
通讯作者:
Grune, T
Grune, T
中科院分区:
生物学3区
文献类型:
--
作者:
Stolzing, A;Wengner, A;Grune, T

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在活的生物体中,发生蛋白质氧化的永久氧化。细胞内氧化蛋白的降解被深入研究,但有关氧化修饰的细胞外蛋白的命运的知识仍然有限。我们研究了外源性添加的氧化蛋白在小胶质细胞中的命运。原代小胶质细胞和RAW细胞都能够从细胞外环境中去除添加的氧化层粘连蛋白和髓鞘碱性蛋白。中度氧化的蛋白质被最有效地降解,而强氧化的蛋白质被小胶质细胞吸收而没有有效的降解。小胶质细胞的活化增强了蛋白酶对中度氧化蛋白底物的选择性识别和降解。抑制剂的研究也揭示了参与的溶酶体和蛋白酶体系统的细胞外蛋白的降解。这些研究让我们得出结论,小胶质细胞能够从大脑的细胞外环境中去除氧化蛋白。(C)2002年爱思唯尔科学(美国)。All rights reserved.
In living organisms a permanent oxidation of protein oxidation occurs. The degradation of intracellular oxidized proteins is intensively studied, but knowledge about the fate of oxidatively modified extracellular proteins is still limited. We studied the fate of exogenously added oxidized proteins in microglial cells. Both primary microglial cells and RAW cells are able to remove added oxidized laminin and myelin basic protein from the extracellular environment. Moderately oxidized proteins are degraded most efficiently, whereas strongly oxidized proteins are taken up by the microglial cells without an efficient degradation. Activation of microglial cells enhances the selective recognition and degradation of moderately oxidized protein substrates by proteases. Inhibitor studies also revealed an involvement of the lysosomal and the proteasomal system in the degradation of extracellular proteins. These studies let us conclude that microglial cells are able to remove oxidized proteins from the extracellular environment in the brain. (C) 2002 Elsevier Science (USA). All rights reserved.