细胞生物学
细胞凋亡
异位表达
Notch信号通路
蛋白激酶B
细胞色素c
化学
线粒体
小发夹RNA
生物
信号转导
基因
生物化学
基因敲除
作者
Xuepeng Chen,Song-Ying Li,Zhaobin Zeng,Zhenyong Gu,Yanfang Yu,Fei-Fei Zheng,Yi Zhou,Huiming Wang
标识
DOI:10.1016/j.biocel.2016.11.013
摘要
Dental follicle stem cells (DFSCs) have been considered as promising candidate cells for periodontal tissue regeneration. Understanding the signalling pathways underlying the apoptosis of DFSCs will facilitate its biomedical application. Here we showed that Notch1 signalling could inhibit DFSCs apoptosis because the constitutive overexpression of the intracellular domain of Notch1 (ICN1) promoted proliferation and suppressed apoptosis by inhibiting cytoplasmic mitochondrial membrane depolarization, cytochrome c release and activation of caspase-9 and caspase-3. The survival-promoting effect of Notch1 was also accomplished by up-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1, down-regulation of the pro-apoptotic proteins Bax and Bad, and blockade of Bax multimerization. Moreover, p-Akt (S473) was significantly increased after ectopic Notch 1 activation. The expression of p53 was also inhibited in Notch1-overexpressing DFSCs, while the ectopic expression of p53 promoted apoptosis even when Notch1 was overexpressed. Meanwhile, all of the opposite phenomena were observed in Notch1 shRNA-silenced DFSCs. Our data strongly suggested that Notch1 signalling inhibited the apoptosis of DFSCs via the cytoplasmic mitochondrial pathway and ICN-Akt signalling pathway, together with nuclear gene expression regulation. These findings would provide molecular cues for the further medical application of DFSCs.
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