Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, 3201, South Africa.
Department of Human Biology and Human Genetics, Technical University of Kaiserslautern, 67663, Kaiserslautern, Germany.
Mol Biol Rep. 2020 Apr;47(4):3019-3024. doi: 10.1007/s11033-020-05364-z. Epub 2020 Mar 9.
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.
甘油醛-3-磷酸脱氢酶（GAPDH）对细胞氧化应激的促凋亡反应疑似与阿尔茨海默病（AD）有关。有趣的是，淀粉样前体蛋白（APP）的过表达可以在哺乳动物细胞系中引发氧化应激反应。在这里，APP695 和 APP770 的过表达显著增加了 GAPDH 的水平，而当使用 APP 同源物 APLP1 或 APLP2 时则没有观察到这种效果。APP695 的异源表达显示，细胞质中的 GAPDH 水平增加了 100%以上，线粒体中的 GAPDH 水平增加了约 50%。此外，在对照细胞系中观察到细胞器从细胞质>细胞核>线粒体的分布转移到 APP695 过表达细胞系中的细胞质>线粒体>细胞核。此外，APP695 的过表达将 GAPDH 聚集温度提高了 3.09±0.46°C，表明热稳定性更高。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。
