Amyloid beta peptide induces cytochrome C release from isolated mitochondria.
Amyloid beta peptide (Abeta) is a neurotoxic metabolic product of the amyloid precursor protein (APP). Abeta is strongly implicated in the pathology of Alzheimer's disease (AD) and can be formed intracellularly. In this study, we show that the addition of Abeta to isolated mouse brain mitochondria can directly induce cytochrome c (Cyt c) release and mitochondrial swelling, which were partially inhibited by cyclosporin A (CsA). These results suggest that the Abetaaccumulated intracellularly by APP processing might exert neurotoxicity by interacting with mitochondria and inducing mitochondrial swelling and release of Cyt c, which activates caspase-3 and finally can lead to apoptosis in neuronal cells and to neurodegeneration in AD.
Kim
Hye-Sun
HS
Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul 110-799, South Korea.
Lee
Jun-Ho
JH
Lee
Jean-Pyo
JP
Kim
Eun-Mee
EM
Chang
Keun-A
KA
Park
Cheol Hyoung
CH
Jeong
Sung-Jin
SJ
Wittendorp
M C
MC
Seo
Ji-Heui
JH
Choi
Se-Hoon
SH
Suh
Yoo-Hun
YH
D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity
D016229:Amyloid beta-Peptides; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016572:Cyclosporine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases