Toxoplasma gondii induces autophagy and apoptosis in human umbilical cord mesenchymal stem cells via downregulation of Mcl-1
Toxoplasma gondii induces autophagy and apoptosis in human umbilical cord mesenchymal stem cells via downregulation of Mcl-1
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DOI：
10.1080/15384101.2017.1281484
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Quan, Juan-Hua
中科院分区：
文献类型：
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作者：
Chu, Jia-Qi;Jing, Kai-Peng;Quan, Juan-Hua
自噬和细胞凋亡是控制弓形虫的关键。弓形虫）感染。T.怀孕期间感染弓形虫可损害胎儿并导致出生缺陷;然而，对这一过程的分子机制知之甚少。本研究旨在探讨T.通过使用人脐带间充质干细胞（hUC-MSCs）作为先天性疾病的模型，自噬的标志蛋白LC 3B随着感染时间的延长而逐渐上调，而p62在T.感染弓形虫的hUC-MSCs。与此同时，T. hUC-MSCs中弓形虫的表达呈时间依赖性增加。Bcl-2家族蛋白Bcl-2、Bcl-xL、Bim、Bax、Bid和巴克的表达水平没有改变，而Mcl-1的表达水平在T.弓形虫感染此外，在感染后24小时，hUC-MSC中裂解的PARP和裂解的半胱天冬酶-3蛋白水平升高。重要的是，Mcl-1过表达降低了T.感染弓形虫的hUC-MSCs。Mcl-1蛋白主要表达在含有线粒体的组分中，并且在正常条件下与Beclin-1强烈相互作用;然而，这些相互作用被T.弓形虫感染这些结果表明，线粒体Mcl-1是调节T.弓形虫感染
Autophagy and apoptosis are critical for controlling Toxoplasma gondii (T. gondii) infection. T. gondii infection during pregnancy can damage the fetus and cause birth defects; however, the molecular mechanisms of this process are poorly understood. This study aims to determine the activities of autophagy and apoptosis as well as their regulatory mechanisms during T. gondii infection by using human umbilical cord mesenchymal stem cells (hUC-MSCs) as a model of congenital diseases. LC3B, a hallmark protein of autophagy was incrementally upregulated with the infection duration, whereas p62 was downregulated in T. gondii-infected hUC-MSCs. Concurrent to this result, the invasion of T. gondii into hUC-MSCs increased in a time-dependent manner. The expression levels of Bcl-2 family proteins including Bcl-2, Bcl-xL, Bim, Bax, Bid and Bak were not altered; however, Mcl-1 levels in hUC-MSCs were dramatically decreased upon T. gondii infection. In addition, at 24h post-infection, cleaved PARP and cleaved caspase-3 protein levels were elevated in hUC-MSCs. Importantly, Mcl-1 overexpression reduced the levels of autophagy- and apoptosis-related proteins in T. gondii-infected hUC-MSCs. Mcl-1 proteins were primarily expressed in the fraction containing mitochondria and strongly interacted with Beclin-1 under normal conditions; however, these interactions were remarkably attenuated by T. gondii infection. These results suggest that mitochondrial Mcl-1 is an essential signaling mediator regulating the activation of autophagy and apoptosis during T. gondii infection.