The amyloid precursor protein intracellular domain alters gene expression and induces neuron-specific apoptosis.
The amyloid precursor protein intracellular domain alters gene expression and induces neuron-specific apoptosis.
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DOI：
10.1016/j.gene.2010.11.014
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发表时间：
2011-04
期刊：
影响因子：
3.5
通讯作者：
Takeshi Ohkawara;H. Nagase;C. Koh;K. Nakayama
中科院分区：
文献类型：
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作者：
Takeshi Ohkawara;H. Nagase;C. Koh;K. Nakayama
虽然淀粉样前体蛋白(APP)在阿尔茨海默病中起核心作用，但该蛋白的生理功能尚未完全阐明。根据先前的报道，我们建立了一个表达APP胞内区(AICD)的胚胎癌细胞系P19。当用维甲酸处理这些细胞系分化出神经元时，AICD的表达诱导了神经元特异性的凋亡。作为确定参与这一过程的基因的第一步，我们评估了AICD通过细胞死亡诱导的基因表达的变化。通过DNA微阵列分析检测41,256个转录本的表达水平。在AICD存在的情况下，277个基因的表达上调了10倍以上。相反，341个基因的表达出现下调，不到原始水平的十分之一。选择的17个基因的逆转录-聚合酶链式反应与芯片结果显示出很好的一致性。这些结果提示，AICD可诱导基因表达的动态变化，这可能与AICD诱导的神经元特异性凋亡密切相关。
Although amyloid precursor protein (APP) plays a central role in Alzheimer's disease, the physiological functions of this protein have yet to be fully elucidated. As previously reported, we established an embryonic carcinoma P19 cell line expressing the intracellular domain of APP (AICD). While neurons were differentiated from these cell lines with retinoic acid treatment, expression of AICD induced neuron-specific apoptosis. As the first step to identify the genes involved in this process, we evaluated AICD-induced changes in gene expression through cell death. The levels of expression of 41,256 transcripts were monitored by DNA microarray analysis. The expression of 277 genes showed up-regulation by more than 10-fold in the presence of AICD. Conversely, the expression of 341 genes showed down-regulation to less than one-tenth of the original level. Reverse transcription-polymerase chain reaction of 17 selected genes showed excellent agreement with the microarray results. These results suggest that AICD induces dynamic changes in gene expression, which may be closely correlated with AICD-induced neuron-specific apoptosis.