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Silibinin ameliorats H2O2-induced cell apoptosis and oxidative stress response by activating Nrf2 signaling in trophoblast cells
Acta Histochemica ( IF 2.5 ) Pub Date : 2020-10-14 , DOI: 10.1016/j.acthis.2020.151620
Hui Guo 1 , Ying Wang 2 , Di Liu 1
Affiliation  

Preeclampsia is a pregnancy-specific syndrome and is one of the major causes of maternal mortality around the world. Cell apoptosis and oxidative stress are involved in development of preeclampsia. Silibinin has been known with anti-inflammatory, anti-oxidative and anti-tumor roles. In this study, hydrogen peroxide (H2O2) administration induced apoptosis in HTR-8/SVneo trophoblast cells, evidenced by decreased level of Bcl-2 and increased levels of Bax and cleaved caspase-3. Western blot and JC-1 staining revealed that H2O2 led to decline of mitochondrial membrane potential (Δψm) and release of cytochrome C from mitochondria to cytoplasm. H2O2 also resulted in reactive oxygen species production and oxidative stress response, evidenced by elevated levels of malondialdehyde, and reduced activity of superoxide dismutase and glutathione peroxidase. Silibinin suppressed H2O2-induced apoptosis, decrease of Δψm and oxidative stress response. In addition, immunofluorescent staining and electrophoretic mobility shift assay demonstrated that H2O2 enhanced expression and nuclear translocation of nuclear factor-erythroid 2-like 2 (Nrf2), and the expression levels of heme oxygenases-1 and quinone oxidoreductase 1 were increased, suggesting the activation of Nrf2 signaling. The activity of Nrf2 signaling was further promoted by silibinin administration. Interestingly, the effect of silibinin on apoptosis and oxidative stress was abolished by interference RNA of Nrf2. In conclusion, we demonstrated that silibinin ameliorated H2O2-induced apoptosis and oxidative stress response by activating Nrf2 signaling in trophoblast cells. These findings may provide novel insights for treatment of preeclampsia.



中文翻译:

水飞蓟宾通过激活滋养层细胞中的 Nrf2 信号来改善 H2O2 诱导的细胞凋亡和氧化应激反应

先兆子痫是一种妊娠特有的综合征,是全世界孕产妇死亡的主要原因之一。细胞凋亡和氧化应激参与子痫前期的发展。已知水飞蓟宾具有抗炎、抗氧化和抗肿瘤作用。在这项研究中,过氧化氢 (H 2 O 2 ) 给药诱导 HTR-8/SVneo 滋养层细胞凋亡,这可以通过 Bcl-2 水平降低和 Bax 和裂解的 caspase-3 水平增加来证明。Western印迹和JC-1染色显示H 2 O 2导致线粒体膜电位(Δψm)下降和细胞色素C从线粒体释放到细胞质。H 2 O 2还导致活性氧的产生和氧化应激反应,这可以通过丙二醛水平升高以及超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低来证明。水飞蓟宾抑制 H 2 O 2诱导的细胞凋亡、Δψm 的降低和氧化应激反应。此外,免疫荧光染色和电泳迁移率变化试验表明 H 2 O 2核因子-类红细胞 2 样 2 (Nrf2) 的表达和核转位增强,血红素加氧酶-1 和醌氧化还原酶 1 的表达水平增加,表明 Nrf2 信号传导激活。水飞蓟宾给药进一步促进了 Nrf2 信号传导的活性。有趣的是,Nrf2 的干扰 RNA 消除了水飞蓟宾对细胞凋亡和氧化应激的影响。总之,我们证明水飞蓟宾通过激活滋养层细胞中的 Nrf2 信号传导来改善 H 2 O 2诱导的细胞凋亡和氧化应激反应。这些发现可能为治疗先兆子痫提供新的见解。

更新日期:2020-10-14
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