Oxidative stress produced by xanthine oxidase induces apoptosis in human extravillous trophoblast cells.
Oxidative stress produced by xanthine oxidase induces apoptosis in human extravillous trophoblast cells.
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DOI：
10.1262/jrd.2012-053
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Wake N
中科院分区：
文献类型：
--
作者：
Murata M;Fukushima K;Takao T;Seki H;Takeda S;Wake N
氧化应激已被认为是先兆子痫的病理生理学的一个重要因素。已有研究表明，子痫前期患者胎盘滋养层细胞黄嘌呤氧化酶（XO）的表达及血浆过氧化氢（H2 O2）水平明显高于正常对照组。本研究的目的是阐明XO产生的活性氧对绒毛外滋养层细胞（EVT）的生物学影响。TCL 1细胞，一种人永生化EVT细胞系，与黄嘌呤和XO（X/XO）一起孵育。然后，我们测量了细胞数量，培养基中的尿酸盐水平和凋亡细胞比率。类似的实验进行了额外的管理别嘌呤醇，过氧化氢酶，L-NAME或D-NAME，并与管理H2 O2的替代X/XO。我们评估了H2 O2对TCL 1的侵袭能力、管状形成以及HIF 1A和ITGAV蛋白表达的影响。最后，使用原代培养的滋养层细胞的凋亡细胞比率进行测量后暴露于H2 O2。X/XO可显著降低细胞相对数量，增加尿酸水平和凋亡细胞比例。别嘌呤醇和过氧化氢酶分别减弱尿酸水平和凋亡细胞比率的升高。L-NAME和D-NAME对上述效应无影响。H_2O_2也使相对细胞数减少。H_2O_2预处理可显著抑制TCL_1细胞的侵袭能力、管状结构的形成以及HIF 1A和ITGAV的表达。H_2O_2还可诱导原代培养的滋养层细胞凋亡。总之，XO产生的ROS诱导细胞凋亡，影响EVT的功能，包括侵袭和分化。
Oxidative stress has been recognized as an important factor in the pathophysiology of preeclampsia. It has been reported that the expression of xanthine oxidase (XO) in the cytotrophoblast and plasma hydrogen peroxide (H2O2) level are significantly higher in preeclamptics than in control women. The aim of this study was to clarify the biological influence of reactive oxygen species (ROS) produced by XO on extravillous trophoblast (EVT) cells. TCL1 cells, a human immortalized EVT cell line, were incubated with xanthine and XO (X/XO). We then measured the cell number, urate level of the culture media and the apoptotic cell ratio. Similar experiments were performed with additional administration of allopurinol, catalase, L-NAME or D-NAME, and with administration of H2O2 in substitution for X/XO. We assessed the effects of H2O2 on invasion ability, tube-like formation and protein expression of HIF1A and ITGAV of TCL1. Finally, the apoptotic cell ratio using primary cultured trophoblasts was measured following exposure to H2O2. X/XO decreased the relative cell number and increased the urate level and apoptotic cell ratio significantly. Elevation of the urate level and apoptotic cell ratio was attenuated by allopurinol and catalase, respectively. L-NAME and D-NAME had no influence on these effects. H2O2 also decreased the relative cell number. Pretreatment with H2O2 significantly inhibited the invasion ability, tube-like formation and HIF1A and ITGAV of TCL1. H2O2 also induced apoptosis in primary cultured trophoblasts. In conclusion, ROS produced by XO induced apoptosis and affected EVT function including invasion and differentiation.
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DOI：
10.1083/jcb.113.2.437
发表时间：
1991-04
期刊：
The Journal of cell biology
影响因子：
--
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Librach CL;Werb Z;Fitzgerald ML;Chiu K;Corwin NM;Esteves RA;Grobelny D;Galardy R;Damsky CH;Fisher SJ
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