Cathepsin D is one of the major enzymes involved in intracellular degradation of AGE-modified proteins
Cathepsin D is one of the major enzymes involved in intracellular degradation of AGE-modified proteins
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DOI：
10.3109/10715762.2010.495127
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发表时间：
2010-09-01
影响因子：
3.3
通讯作者：
Grune, Tilman
中科院分区：
文献类型：
--
作者：
Grimm, Stefanie;Ernst, Lisa;Grune, Tilman
氧化和交联化的修饰蛋白在老化过程中会积累。对于晚期糖基化终产物(AGEs)修饰的蛋白质的积累是否由于受影响的细胞内降解而知之甚少。因此，本研究旨在确定细胞内酶组织蛋白酶B、组织蛋白酶D和20S蛋白酶体是否能够在体外降解AGE修饰的蛋白质。结果表明，AGE修饰的白蛋白被组织蛋白酶D降解，而组织蛋白酶B对醛修饰的白蛋白的降解效果较差，20S蛋白酶体完全不能降解它们。从组织蛋白酶D基因敲除动物中分离的小鼠原代胚胎成纤维细胞与从野生型动物中分离的细胞相比，发现有广泛的细胞内AGE积聚，主要是在溶酶体中，并且AGE修饰的蛋白质降解减少。综上所述，可以假设组织蛋白酶D在去除AGE修饰的蛋白质方面起着重要作用。
Oxidized and cross-linked modified proteins are known to accumulate in ageing. Little is known about whether the accumulation of proteins modified by advanced glycation end products (AGEs) is due to an affected intracellular degradation. Therefore, this study was designed to determine whether the intracellular enzymes cathepsin B, cathepsin D and the 20S proteasome are able to degrade AGE-modified proteins in vitro. It shows that AGE-modified albumin is degraded by cathepsin D, while cathepsin B was less effective in the degradation of aldehyde-modified albumin and the 20S proteasome was completely unable to degrade them. Mouse primary embryonic fibroblasts isolated from a cathepsin D knockout animals were found to have an extensive intracellular AGE-accumulation, mainly in lysosomes, and a reduction of AGE-modified protein degradation compared to cells isolated from wild type animals. In summary, it can be assumed that cathepsin D plays a significant role in the removal of AGE-modified proteins.