Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent.
Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.
Choi
S I
SI
Institute of Environment & Life Science and Department of Microbiology, College of Medicine, Hallym University, Chunchon, Korea. de1951@sun.hallym.ac.kr
Ju
W K
WK
Choi
E K
EK
Kim
J
J
Lea
H Z
HZ
Carp
R I
RI
Wisniewski
H M
HM
Kim
Y S
YS
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D002374:Catalase / Q000032:analysis; D006224:Cricetinae; D003600:Cytosol / Q000737:chemistry; D003576:Electron Transport Complex IV / Q000032:analysis; D004789:Enzyme Activation; D005260:Female; D005979:Glutathione Peroxidase / Q000032:analysis; D005980:Glutathione Reductase / Q000032:analysis; D015227:Lipid Peroxidation; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress; D017096:Prion Diseases; D017382:Reactive Oxygen Species / Q000502:physiology; D012608:Scrapie / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000032:analysis
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases