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Influence of Oxidative Stress on D ‐Aspartyl Endopeptidase Activity
Author(s) -
Kinouchi Tadatoshi,
Matsuda Akina,
Kawakami Satoru,
Shimizu Takahiko,
Shirasawa Takuji,
Fujii Noriko
Publication year - 2010
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200900345
Subject(s) - chemistry , oxidative stress , biochemistry , mitochondrion , oxidative phosphorylation , reactive oxygen species , prolyl endopeptidase , neprilysin , endopeptidase , protease , protein aggregation , enzyme
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.