Zhao B, Chrest F J, Horton W E, Sisodia S S, Kusiak J W
Molecular Neurobiology Unit/LBC, National Institute on Aging, Baltimore, Maryland 21224, USA.
J Neurosci Res. 1997 Feb 1;47(3):253-63.
The cause of neuronal loss in Alzheimer disease is unknown. We investigated the effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant amyloid precursor proteins (APP). Differentiated cells expressing mutant APPs exhibited somal shrinkage, followed by cell detachment from the plates. Increased levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were observed, and electron microscopy revealed extensive plasma membrane blebbing, margination of condensed chromatin, and well-preserved organelles in these transfectants. The levels of TUNEL-positive cells, analyzed by a flow-cytometric method, were increased by four- to sevenfold in mutant APP transfectants, but less than twofold in wild-type APP transfectants relative to untransfected cells. Our results provide evidence that expression of mutant APPs in differentiated PC12 cells induces cell death via an apoptotic pathway.
阿尔茨海默病中神经元丧失的原因尚不清楚。我们研究了表达A692G、E693Q和V717F突变淀粉样前体蛋白（APP）对PC12细胞存活的影响。表达突变APP的分化细胞表现出细胞体萎缩，随后细胞从平板上脱离。观察到寡核小体大小的DNA梯带水平增加以及TUNEL阳性细胞核增多，电子显微镜显示这些转染细胞中存在广泛的质膜泡状化、浓缩染色质边缘化以及保存完好的细胞器。通过流式细胞术分析，突变APP转染细胞中TUNEL阳性细胞水平相对于未转染细胞增加了4至7倍，而野生型APP转染细胞中增加不到2倍。我们的结果提供了证据，表明分化的PC12细胞中突变APP的表达通过凋亡途径诱导细胞死亡。
