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首页> 外文期刊>Infection and immunity >Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice
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Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice

机译：活性氧触发的滋养细胞凋亡是由内质网应激通过激活弓形体弓形虫感染的Caspase-12，CHOP和JNK途径引起的内质网应激引起的。

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Toxoplasma gondii infection in pregnant women may result in abortion or in fetal teratogenesis; however, the underlying mechanisms are still unclear. In this paper, based on a murine model, we showed that maternal infection with RH strain T. gondii tachyzoites induced elevated production of reactive oxygen species (ROS), local oxidative stress, and subsequent apoptosis of placental trophoblasts. PCR array analysis of 84 oxidative stress-related genes demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were downregulated at least 2-fold in the T. gondii infection group compared with levels in the control group. The expression of NADPH oxidase 1 (Nox1) and glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased significantly with T. gondii infection, and levels of glutathione (GSH) decreased rapidly. T. gondii infection increased the early expression of endoplasmic reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of ASK1/JNK, and increased apoptosis of trophoblasts, both in vivo and in vitro. The apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway, and the production of peroxides were dramatically inhibited by pretreatment with N-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and preceded the increase in levels of ERS markers and the activation of the proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts was initiated predominantly by ROS-mediated ERS via activation of caspase-12, CHOP, and the JNK pathway in acute T. gondii infection. Elevated ROS production is the central event in T. gondii-induced apoptosis of placental trophoblasts.
机译：孕妇弓形虫感染可能导致流产或胎儿畸胎;但是，其潜在机制仍不清楚。在本文中，基于鼠模型，我们显示产妇感染RH菌株T. gondii速殖子会引起活性氧（ROS）的产生升高，局部氧化应激以及随后的胎盘滋养细胞凋亡。 PCR阵列分析了84个氧化应激相关基因，与对照组相比，弓形虫感染组中27个基因上调了至少2倍，而9个基因下调了至少2倍。 NADPH氧化酶1（Nox1）和谷胱甘肽过氧化物酶6（Gpx6）的表达显着增加，约为25倍。刚地弓形虫感染导致丙二醛（MDA）和8-羟基脱氧鸟苷（8-OHdG）的含量显着增加，而谷胱甘肽（GSH）的含量则迅速下降。刚地弓形虫感染在体内和体外均增加了内质网应激（ERS）标记的早期表达，随后裂解caspase-12，激活ASK1 / JNK并增加了滋养细胞的凋亡。用N-乙酰半胱氨酸（NAC）预处理可显着抑制滋养层细胞的凋亡，caspase-12的活化和ASK1 / JNK途径以及过氧化物的产生。 Nox1的上调是依赖接触的，并且在ERS标志物水平增加和促凋亡级联反应激活之前。因此，我们得出结论，在急性弓形虫感染中，胎盘滋养细胞的凋亡主要是由ROS介导的ERS通过激活caspase-12，CHOP和JNK途径引起的。 ROS的产生是弓形虫诱导的胎盘滋养细胞凋亡的中心事件。

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