Environmental Mutagens and Carcinogens (한국환경성돌연변이발암원학회지)
- Volume 25 Issue 1
- /
- Pages.19-24
- /
- 2005
- /
- 1225-6307(pISSN)
Alzheimer's Disease-linked Swedish Amyloid Precursor Protein Mutation Induces Cell Death by Increasing Reactive Oxygen Species Generation
- Kim Hye Sun (Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute) ;
- Lee Jun Ho (Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute) ;
- Kim Eun Mee (Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute) ;
- Lee Jean Pyo (Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute) ;
- Suh Yoo Hun (Department of Cell Biology, Harvard Medical School)
- Published : 2005.03.01
Abstract
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/A/3 mediated neurotoxicity is observed both in vitro and in vivo, the relationship between mutant APP expression, A/3 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.
Keywords