School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast Campus, Southport, QLD, Australia.
Placenta. 2013 Jul;34(7):594-8. doi: 10.1016/j.placenta.2013.04.010. Epub 2013 May 6.
Oxidative stress plays an important role in the pathogenesis of preeclampsia, a placental disorder affecting approximately 7% of pregnancies. Trophoblast cells are susceptible to oxidative stress which causes increased cell death and placental turnover. In this study, inhibitors of the mitochondrial respiratory chain were utilised to induce oxidative stress and the effect that selenium supplementation had on trophoblast viability was investigated.
Trophoblast cells (BeWo, JEG-3 and Swan-71) were treated with Na Selenite (100 nM) or Selenomethionine (500 nM) to increase the biological activity of antioxidants Glutathione Peroxidase and Thioredoxin Reductase. The cells were then oxidatively stressed with the addition of increasing doses of Antimycin C and Rotenone and the Resazurin end point assay was used to assess cellular activity.
There was a significant dose dependent decrease in the cellular activity in BeWo, JEG-3 and Swan-71 when treated for 4 h with increasing concentrations of Antimycin (40-320 μM) and Rotenone (100-800 nM). Prior incubation with Na Selenite and Selenomethionine was able to protect trophoblast cells from oxidative stress at Rotenone concentrations of 200 and 400 nM (P < 0.001) and Antimycin concentrations of 80-240 μM (P < 0.001).
These data suggest that selenoproteins such as Glutathione Peroxidase and Thioredoxin Reductase have an important role in protecting trophoblast mitochondria from oxidative stress.
This study emphasises the importance of maintaining an adequate selenium supply during pregnancy and especially in pregnancies complicated by conditions such as preeclampsia.
氧化应激在子痫前期(一种影响约 7%妊娠的胎盘疾病)的发病机制中起着重要作用。滋养细胞容易受到氧化应激的影响,这会导致细胞死亡增加和胎盘更新。在这项研究中,利用线粒体呼吸链抑制剂来诱导氧化应激,并研究硒补充对滋养细胞活力的影响。
用亚硒酸钠(100 nM)或硒蛋氨酸(500 nM)处理滋养细胞(BeWo、JEG-3 和 Swan-71),以增加抗氧化剂谷胱甘肽过氧化物酶和硫氧还蛋白还原酶的生物活性。然后,用增加剂量的安密霉素 C 和鱼藤酮对细胞进行氧化应激,并用 Resazurin 终点测定法评估细胞活性。
BeWo、JEG-3 和 Swan-71 细胞在 4 小时内用增加浓度的安密霉素(40-320 μM)和鱼藤酮(100-800 nM)处理时,细胞活性呈显著剂量依赖性下降。预先用亚硒酸钠和硒蛋氨酸孵育可以保护滋养细胞免受鱼藤酮浓度为 200 和 400 nM(P < 0.001)和安密霉素浓度为 80-240 μM(P < 0.001)的氧化应激。
这些数据表明,谷胱甘肽过氧化物酶和硫氧还蛋白还原酶等硒蛋白在保护滋养细胞线粒体免受氧化应激方面起着重要作用。
本研究强调了在怀孕期间,特别是在子痫前期等疾病复杂的情况下,维持足够的硒供应的重要性。