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KMID : 0382320050250010019
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Environmental Mutagens and Carcinogens
2005 Volume.25 No. 1 p.19 ~ p.24
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Alzheimer’s Disease-linked Swedish Amyloid Precursor Protein Mutation Induces Cell Death by Increasing Reactive Oxygen Species Generation
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Kim HS
Lee JH/Kim EM/Lee JP/Suh YH
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Abstract
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The Swedish double mutation (KM670/671NL) of amyloid precursor protein (Swe-APP) is associated with early-onset familial Alzheimer’s disease (FAD) and increases amyloid beta peptide production. Although APP/Aβ mediated neurotoxicity is observed both in vitro and in vivo, the relationship between mutant APP expression, Aβ production, and neuronal death observed in the brains of FAD patients remains to be elucidated. In this study, we investigated the mechanisms of Swe-APP-induced cell death in HEK293 and NGF-differentiated PC 12 cells. We found that the expression of Swe-APP induced cytochrome C relase, activation of caspase 3 in HEK 293 and NGF-differentiated PC 12 cells. We also show that the reactive oxygen species (ROS) was detected in Swe-APP expressing HEK 293 cells and NGF-differentiated PC 12 cells and that pretreatment with vitamine E attenuated the cellular death, cytochrome C release induced by Swe-APP expression, indicating the involvement of free radical in these processes. These results suggest one of possible apoptotic mechanisms of Swe-APP which could occur through cytochrome C release from mitochondria and this apoptosis inducing effects could be at least in part, due to ROS generation by Swe-APP expression.
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KEYWORD
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