Influence of oxidative stress on D-aspartyl endopeptidase activity.

Tadatoshi Kinouchi, Akina Matsuda, Satoru Kawakami, Takahiko Shimizu, Takuji Shirasawa, Noriko Fujii

Divison of Radiation Life Science, Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka 590-0494, Japan. kinouchi@rri.kyoto-u.ac.jp

Chemistry & biodiversity 2010 Jun

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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.

Citation

Tadatoshi Kinouchi, Akina Matsuda, Satoru Kawakami, Takahiko Shimizu, Takuji Shirasawa, Noriko Fujii. Influence of oxidative stress on D-aspartyl endopeptidase activity. Chemistry & biodiversity. 2010 Jun;7(6):1398-402