Elevated nitric oxide production mediates beta-amyloid-induced mitochondria failure.
Mitochondrial dysfunction has been identified in a large proportion of neurodegenerative disorders including Alzheimer's disease (AD). In addition, the involvement of nitric oxide (NO) has been implicated in the pathogenesis of AD. Thus, we investigated the effects of the Swedish double mutation (K670M/N671L) in the beta-amyloid precursor protein (APPsw) on NO levels and mitochondrial function in PC12 cells. Interestingly, APPsw PC12 cells showed increased NO levels, decreased cytochrome C oxidase activity and reduced ATP levels compared to wild-type APP bearing cells and empty vector transfected cells. On the basis of our data, we propose a hypothetical sequence of events linking amyloid beta-peptide and NO production with mitochondria failure.
Keil
U
U
Department of Pharmacology, Biocenter, University of Frankfurt, 60439 Frankfurt/Main, Germany.
Bonert
A
A
Marques
C A
CA
Strosznajder
J B
JB
Müller-Spahn
F
F
Müller
W E
WE
Eckert
A
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology*
D016229:Amyloid beta-Peptides; D009569:Nitric Oxide