Characterization of mitochondrial dysfunction in the 7PA2 cell model of Alzheimer's disease.
The 7WD4 and 7PA2 cell lines, widely used as cellular models for Alzheimer's disease (AD), have been used to investigate the effects of amyloid-β protein precursor overexpression and amyloid-β (Aβ) oligomer accumulation on mitochondrial function. Under standard culture conditions, both cell lines, compared to Chinese hamster ovary (CHO) control cells, displayed an ~5% decrease of O2 respiration as sustained by endogenous substrates. Functional impairment of the respiratory chain was found distributed among the protein complexes, though more evident at the level of complex I and complex IV. Measurements of ATP showed that its synthesis by oxidative phosphorylation is decreased in 7WD4 and 7PA2 cells by ~25%, this loss being partly compensated by glycolysis (Warburg effect). Compensation proved to be more efficient in 7WD4 than in 7PA2 cells, the latter cell line displaying the highest reactive oxygen species production. The strongest deficit was observed in mitochondrial membrane potential that is almost 40% and 60% lower in 7WD4 and 7PA2 cells, respectively, in comparison to CHO controls. All functional parameters point to a severe bioenergetic impairment of the AD cells, with the extent of mitochondrial dysfunction being correlated to the accumulation of Aβ peptides and oligomers.
Scuola Normale Superiore, Pisa, Italy European Brain Research Institute - "Rita Levi-Montalcini", Rome, Italy.
Nina
N
Krako
Maria Chiara
MC
Magnifico
Marzia
M
Arese
Giovanni
G
Meli
Elena
E
Forte
Agnese
A
Lecci
Annalisa
A
Manca
Alessandro
A
Giuffrè
Daniela
D
Mastronicola
Paolo
P
Sarti
Antonino
A
Cattaneo
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species
Alzheimer's disease; amyloid-β oligomers; bioenergetics; mitochondrial dysfunction