Influence of oxidative stress on D-aspartyl endopeptidase activity.
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.
Kinouchi
Tadatoshi
T
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
Matsuda
Akina
A
Kawakami
Satoru
S
Shimizu
Takahiko
T
Shirasawa
Takuji
T
Fujii
Noriko
N
D000375:Aging; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
D016282:Aspartic Acid Endopeptidases; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse