Toxoplasma gondii isolate with genotype Chinese 1 triggers trophoblast apoptosis through oxidative stress and mitochondrial dysfunction in mice
Toxoplasma gondii isolate with genotype Chinese 1 triggers trophoblast apoptosis through oxidative stress and mitochondrial dysfunction in mice
复制标题
基因型Chinese 1的弓形虫分离株通过氧化应激和线粒体功能障碍触发小鼠滋养层细胞凋亡
DOI：
10.1016/j.exppara.2015.04.008
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发表时间：
2015-07-01
影响因子：
2.1
通讯作者：
Shen, Jilong
中科院分区：
文献类型：
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作者：
Xu, Xiucai;He, Liuyuan;Shen, Jilong
先天性弓形虫病可能会导致流产、严重的智力低下和后代的神经损伤。胎盘损害被认为是本病的关键事件。在这里，我们发现弓形虫中国1型流行株Wh3株感染母体可诱导孕鼠滋养层细胞凋亡。对84个影响小鼠线粒体生物发生和功能的关键基因的PCR芯片分析表明，与对照组相比，Wh3感染组中有10个基因上调了至少2倍。感染组小鼠血中活性氧(ROS)、丙二醛(MDA)、8-羟基脱氧鸟苷(8-OHdG)含量升高，谷胱甘肽(GSH)含量降低。NADPH氧化酶1和谷胱甘肽过氧化物酶6(GPx6)的mRNA水平显著升高。过量的ROS产生依赖于NADPH氧化酶，导致胎盘线粒体结构破坏和线粒体功能障碍，进而导致caspase-9和caspase-3的裂解，最终导致滋养层细胞的凋亡。给予抗氧化剂N-乙酰半胱氨酸(NAC)可抑制上述现象的发生。综上所述，我们得出结论，妊娠期间Wh3感染可能通过氧化应激诱导的线粒体功能障碍和下游信号通路的激活而促进滋养层细胞的凋亡。(C)2015 Elsevier Inc.保留所有权利。
Congenital toxoplasmosis may result in abortion, severe mental retardation and neurologic damage in the offspring. Placental damage is considered as the key event in this disease. Here we show that maternal infection with Toxoplasma gondii Wh3 isolate of genotype Chinese 1, which is predominantly prevalent in China, induced trophoblast apoptosis of pregnant mouse. PCR array analysis of 84 key genes in the biogenesis and functions of mouse mitochondrion revealed that ten genes were up-regulated at least 2-fold in the Wh3 infection group, compared with those in the control. The elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG), as well as the decreased glutathione (GSH), were observed in the infected mice. The mRNA levels of NADPH oxidase 1 and glutathione peroxidase 6 (GPx6) were significantly increased. The production of excessive ROS was NADPH oxidase-dependent, which contributed to mitochondrial structural damage and mitochondrial dysfunction in placentas, followed by the cleavage of caspase-9 and caspase-3, and finally resulted in apoptosis of trophoblasts. All the above-mentioned phenomena were inhibited by pretreatment with the antioxidant of N-acetylcysteine (NAC). Taken together, we concluded that Wh3 infection during pregnancy may contribute to trophoblast apoptosis by oxidative stress-induced mitochondrial dysfunction and activation of the downstream signaling pathway. (C) 2015 Elsevier Inc. All rights reserved.