Scuola Normale Superiore, Pisa, Italy European Brain Research Institute - "Rita Levi-Montalcini", Rome, Italy.
J Alzheimers Dis. 2013;37(4):747-58. doi: 10.3233/JAD-130728.
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.
7WD4 和 7PA2 细胞系被广泛用作阿尔茨海默病（AD）的细胞模型，用于研究淀粉样蛋白-β 前体蛋白过表达和淀粉样蛋白-β（Aβ）寡聚体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，这两种细胞系的内源性底物支持的 O2 呼吸率降低了约 5%。发现呼吸链的功能障碍分布在蛋白复合物中，但在复合物 I 和复合物 IV 中更为明显。ATP 的测量表明，7WD4 和 7PA2 细胞中氧化磷酸化合成的 ATP 减少了约 25%，这一损失部分由糖酵解（Warburg 效应）补偿。在 7WD4 细胞中的补偿效率比在 7PA2 细胞中更高，后者的细胞系显示出最高的活性氧产生。线粒体膜电位的下降最为明显，与 CHO 对照相比，7WD4 和 7PA2 细胞中的线粒体膜电位分别下降了约 40%和 60%。所有功能参数都表明 AD 细胞的生物能量严重受损，线粒体功能障碍的程度与 Aβ 肽和寡聚体的积累相关。
