Divison of Radiation Life Science, Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka 590-0494, Japan.
Chem Biodivers. 2010 Jun;7(6):1398-402. doi: 10.1002/cbdv.200900345.
It is strongly suggested that D-aspartic acid (D-Asp)-containing proteins are spontaneously generated by oxidative stress and would cause many aging-related misfolding diseases, such as cataracts, prion disease, and Alzheimer's disease. We have identified a D-Asp-containing protein-specific protease, D-aspartyl endopeptidase (DAEP), from mammalian mitochondria, serving as a scavenger against the noxious D-Asp-containing protein. Recently, it has been shown that the activity of Lon, an ATP-dependent protease degrading oxidatively damaged proteins in mitochondria, decreases with aging by oxidative stress. However, an obvious relation between DAEP activity and oxidative stress with aging remains to be demonstrated. In the present study, we showed that there was a remarkable decrease in DAEP activity in superoxide dismutase-deficient mice, which formed excess reactive oxygen species (ROS). Our result suggests that a decrease in DAEP activity by oxidative stress may cause the accumulation of D-Asp-containing protein, leading to mitochondria-associated diseases.
强烈建议含 D-天冬氨酸（D-Asp）的蛋白质是由氧化应激自发产生的，会导致许多与衰老相关的错误折叠疾病，如白内障、朊病毒病和阿尔茨海默病。我们已经从哺乳动物线粒体中鉴定出一种含 D-Asp 的蛋白特异性蛋白酶，即 D-天冬氨酸内肽酶（DAEP），它作为一种清除有害的含 D-Asp 蛋白的物质。最近，已经表明 Lon 的活性，一种在线粒体中降解氧化损伤蛋白的 ATP 依赖性蛋白酶，随着氧化应激的衰老而降低。然而，DAEP 活性与衰老时的氧化应激之间的明显关系仍有待证明。在本研究中，我们发现超氧化物歧化酶缺乏的小鼠中 DAEP 活性显著降低，这些小鼠会形成过多的活性氧（ROS）。我们的结果表明，氧化应激导致的 DAEP 活性降低可能会导致含 D-Asp 蛋白的积累，从而导致与线粒体相关的疾病。
