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Effects of U1 Small Nuclear Ribonucleoprotein Inhibition on the Expression of Genes Involved in Alzheimer’s Disease
ACS Omega ( IF 3.7 ) Pub Date : 2020-09-23 , DOI: 10.1021/acsomega.0c03568
Wenbo Zhu 1, 2 , Xuefei Wei 3 , Yanyang Wang 3 , Jingjing Li 4 , Lu Peng 5 , Kui Zhang 1, 2 , Bing Bai 2, 3, 4
Affiliation  

Deposition and dysfunction of U1 small nuclear ribonucleoprotein (snRNP) have been revealed in Alzheimer’s disease (AD), but whether U1 is involved in the amyloid precursor protein (APP) and Tau pathways remains unclear. Here, we investigate this by inhibiting the U1 components in cultured cells and examining the expression changes of AD-related genes to these two canonic pathways. We find that knockdown of U1-70K and U1C increases the protein expressions of APP and GSK-3β while reduces that of Nicastrin in a dose-dependent manner. Knockdown of U1A shows no effects on the expression of these proteins. The real-time PCR results show that the mRNA expression levels of APP, Nicastrin and GSK-3β are unchanged, decreased, and increased, respectively. In addition, U1-70K knockdown suppresses Tau phosphorylation and causes altered splicing of Tau exon 10. This study suggests that the effect of U1 snRNP knockdown is component-specific and more likely involved in APP deregulation in AD.

中文翻译:

U1小核糖核蛋白抑制对阿尔茨海默氏病相关基因表达的影响

U1小核糖核蛋白(snRNP)的沉积和功能障碍已在阿尔茨海默氏病(AD)中发现,但U1是否参与淀粉样前体蛋白(APP)和Tau途径尚不清楚。在这里,我们通过抑制培养细胞中的U1成分并检查AD相关基因到这两个经典途径的表达变化来研究这一点。我们发现,敲低U1-70K和U1C可以增加APP和GSK-3β的蛋白表达,而降低尼卡斯汀的蛋白表达则具有剂量依赖性。击倒U1A对这些蛋白质的表达没有影响。实时PCR结果显示APP,Nicastrin和GSK-3β的mRNA表达水平分别不变,降低和升高。此外,U1-70K敲低抑制Tau磷酸化并导致Tau外显子10的剪接发生改变。
更新日期:2020-10-06
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