Characterization of Mitochondrial Dysfunction in the 7PA2 Cell Model of Alzheimer's Disease
Characterization of Mitochondrial Dysfunction in the 7PA2 Cell Model of Alzheimer's Disease
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DOI：
10.3233/jad-130728
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Cattaneo, Antonino
中科院分区：
文献类型：
--
作者：
Krako, Nina;Magnifico, Maria Chiara;Cattaneo, Antonino
被广泛用作阿尔茨海默病（AD）细胞模型的7WD4和7PA2细胞系已被用于研究淀粉样蛋白- β前体过表达和淀粉样蛋白- β (A β)寡聚物积累对线粒体功能的影响。在标准培养条件下，与中国仓鼠卵巢（CHO）对照细胞相比，这两种细胞系在内源性底物的作用下，O-2呼吸均下降了5%。呼吸链的功能损伤分布在蛋白质复合物中，但在复合物I和复合物IV的水平上更为明显。ATP的测量表明，7WD4和7PA2细胞中通过氧化磷酸化合成的ATP减少了约25%，这种损失部分由糖酵解补偿（Warburg效应）。结果表明，7WD4细胞的补偿效率高于7PA2细胞，后者的活性氧产量最高。与CHO对照组相比，7WD4和7PA2细胞的线粒体膜电位缺陷最大，分别降低了近40%和60%。所有功能参数都表明AD细胞存在严重的生物能损伤，线粒体功能障碍的程度与a β肽和低聚物的积累有关。
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.