Glyceraldehyde 3-phosphate dehydrogenase's (GAPDH) proapoptotic response to cellular oxidative stress has suspected implication for Alzheimer's disease (AD). Interestingly, the overexpression of the amyloid precursor protein (APP) can initiate oxidative stress responses within mammalian cell lines. Here, APP695 and APP770 overexpression significantly increased the level of GAPDH, while no effect was observed when the APP homologues APLP1 or APLP2 were used. Heterologous expression of APP695 was shown to increase the level of GAPDH within the cytoplasm by over 100% and within the mitochondria by approximately 50%. Moreover, a shift in organelle distribution from cytoplasm > nucleus > mitochondria in control cell lines to cytoplasm > mitochondria > nucleus in the APP695 overexpressing cell line was also observed. Further, the overexpression of APP695 increased GAPDH aggregation temperature by 3.09 ± 0.46 °C, indicative of greater thermal stability. These results demonstrate a clear correlation between APP overexpression and GAPDH levels, organelle distribution and thermal stability.

中文翻译：

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淀粉样蛋白前体蛋白影响3-磷酸甘油醛脱氢酶的水平，细胞器的定位和热稳定性。

甘油醛3-磷酸脱氢酶（GAPDH）对细胞氧化应激的促凋亡反应被怀疑与阿尔茨海默氏病（AD）有关。有趣的是，淀粉样蛋白前体蛋白（APP）的过度表达可以启动哺乳动物细胞系内的氧化应激反应。在这里，APP695和APP770的过表达显着增加了GAPDH的水平，而当使用APP的同系物APLP1或APLP2时则未观察到任何作用。显示APP695的异源表达使细胞质内的GAPDH水平增加了100％以上，线粒体内的GAPDH水平增加了约50％。此外，还观察到细胞器分布从控制细胞系中的细胞质>核>线粒体到APP695过表达细胞系中的细胞质>线粒体>核。进一步，APP695的过表达将GAPDH聚集温度提高了3.09±0.46°C，表明具有更高的热稳定性。这些结果表明APP过表达与GAPDH水平，细胞器分布和热稳定性之间存在明显的相关性。