期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 37, 期 4, 页码 747-758出版社
IOS PRESS
DOI: 10.3233/JAD-130728
关键词
Alzheimer's disease; amyloid-beta oligomers; bioenergetics; mitochondrial dysfunction
资金
- Ministero dell'Istruzione, dell'Universita e della Ricerca of Italy [PRIN 20107Z8XBW 005, FIRB RBIN06E9Z8, FIRB RBFR08F41U_001, FIRB RBAP10L8TY]
- Fondazione Roma
- Scuola Normale Superiore
- Alzheimer's Association [NIRG-12-237751]
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-beta protein precursor overexpression and amyloid-beta (A beta) oligomer accumulation on mitochondrial function. Under standard culture conditions, both cell lines, compared to Chinese hamster ovary (CHO) control cells, displayed an similar to 5% decrease of O-2 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 similar to 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 A beta peptides and oligomers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据