Document Detail

Mitochondria dysfunction of Alzheimer's disease cybrids enhances Abeta toxicity.
MedLine Citation:
PMID:  15189344     Owner:  NLM     Status:  MEDLINE    
Alzheimer's disease (AD) brain reveals high rates of oxygen consumption and oxidative stress, altered antioxidant defences, increased oxidized polyunsaturated fatty acids, and elevated transition metal ions. Mitochondrial dysfunction in AD is perhaps relevant to these observations, as such may contribute to neurodegenerative cell death through the formation of reactive oxygen species (ROS) and the release of molecules that initiate programmed cell death pathways. In this study, we analyzed the effects of beta-amyloid peptide (Abeta) on human teratocarcinoma (NT2) cells expressing endogenous mitochondrial DNA (mtDNA), mtDNA from AD subjects (AD cybrids), and mtDNA from age-matched control subjects (control cybrids). In addition to finding reduced cytochrome oxidase activity, elevated ROS, and reduced ATP levels in the AD cybrids, when these cell lines were exposed to Abeta 1-40 we observed excessive mitochondrial membrane potential depolarization, increased cytoplasmic cytochrome c, and elevated caspase-3 activity. When exposed to Abeta, events associated with programmed cell death are activated in AD NT2 cybrids to a greater extent than they are in control cybrids or the native NT2 cell line, suggesting a role for mtDNA-derived mitochondrial dysfunction in AD degeneration.
Sandra M Cardoso; Isabel Santana; Russell H Swerdlow; Catarina R Oliveira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  89     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-10     Completed Date:  2004-07-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1417-26     Citation Subset:  IM    
Laboratory of Biochemistry, Faculty of Medicine and Center for Neurosciences and Cell Biology, University Hospital, University of Coimbra, 3005-504 Coimbra, Portugal.
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MeSH Terms
Alzheimer Disease / enzymology*,  genetics
Amyloid beta-Protein / toxicity*
Caspases / drug effects,  genetics,  metabolism
Cell Line, Tumor
DNA, Mitochondrial / genetics
Electron Transport / drug effects,  genetics
Electron Transport Complex IV / drug effects,  genetics,  metabolism
Hybrid Cells / drug effects*,  metabolism*,  pathology
Lipid Metabolism
Membrane Potentials / drug effects,  genetics
Mitochondria / genetics,  metabolism*,  transplantation
Oxidation-Reduction / drug effects
Oxidative Stress / drug effects,  genetics
Peptide Fragments / toxicity*
Phosphatidylserines / metabolism
Proteins / metabolism
Reactive Oxygen Species / metabolism
Teratocarcinoma / drug therapy,  metabolism*,  pathology
Reg. No./Substance:
0/Amyloid beta-Protein; 0/DNA, Mitochondrial; 0/Peptide Fragments; 0/Phosphatidylserines; 0/Proteins; 0/Reactive Oxygen Species; 0/amyloid beta-protein (1-40); 0/amyloid beta-protein (1-42); EC Transport Complex IV; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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