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在人类体内至少有25种硒蛋白(含有硒代半胱氨酸),啮齿动物体内也已经分离出24种相似的蛋白质,它们在氧化应激,氧化还原调控以及解毒方面发挥重要的作用。无机砷(iAs)暴露调节硒蛋白的表达可能揭示砷毒性的分子机制。为研究iAs暴露对硒蛋白表达的影响,研究者在培养基中添加iAs来调节小鼠胚胎干细胞中已知的含硒蛋白质的表达,小鼠胚胎干细胞分别用亚砷酸盐(iAsⅢ)(0.25～0.5μmol/L)、砷酸盐(iAsⅤ)(1.0～2.0μmol/L),对照亚硒酸钠(SeⅣ)(0.5μmol/L)处理。实时定量PCR检测含硒蛋白质mRNA的表达水平,蛋白免疫印迹分析和酶活性检测来证实硒蛋白的表达上调。结果表明:CGR8干细胞亚砷酸盐(iAsⅢ)(0.25～0.5μmol/L)、砷酸盐(iAsⅤ)(1.0～2.0μmol/L)处理组活性氧自由基(ROS)的产生和核转录因子(Nrf2)的聚集均有显著增加。iAsⅢ(0.5μmol/L)、iAsⅤ(2.μmol/L)处理24 h可引起抗氧化含硒蛋白质(Gpx1、Gpx4、Tr1)的表达显著增加,而硒蛋白H和内质网相关硒蛋白(15-Sep、SelK、SelM、SelS)mRNA的表达显著降低。SeⅣ(0.5μmol/L)处理组未见到明显的硒蛋白表达下调。这些结果表明iAs暴露不仅调节抗氧化硒蛋白而且可以调节内质网弹性相关硒蛋白。但仍需进一步的研究证实这些硒蛋白调节基因是补硒预防无机砷毒性的作用基因。.
There are at least 25 selenoproteins (containing selenocysteine) in humans, and 24 similar proteins have been isolated from rodents that play important roles in oxidative stress, redox regulation and detoxification. Inorganic arsenic (iAs) exposure regulates selenoprotein expression may reveal the molecular mechanism of arsenic toxicity. In order to investigate the effect of iAs exposure on selenoprotein expression, we added iAs to the media to regulate the expression of selenoproteins known in mouse embryonic stem cells. Mouse embryonic stem cells were treated with iAs III (0.25 ~ 0.5μmol / L), arsenate (1.0 ~ 2.0μmol / L) and control selenium (0.5μmol / L). Real-time quantitative PCR was used to detect the expression of selenoprotein mRNA, Western blot analysis and enzymatic activity test to confirm the up-regulation of selenoprotein. The results showed that the production of reactive oxygen species (ROS) and nuclear factor kappa B (NF-κB) in CGR8 stem cells treated with iAsⅢ (0.25 ~ 0.5μmol / L) and arsenate (1.0 ~ 2.0μmol / (Nrf2) aggregation were significantly increased. Treatment with iAsⅢ (0.5μmol / L) and iAsⅤ (2.μmol / L) for 24 h resulted in a significant increase in the expression of antioxidant selenoproteins (Gpx1, Gpx4, Tr1) 15-Sep, SelK, SelM, SelS) mRNA expression was significantly reduced. SeⅣ (0.5μmol / L) treatment group showed no significant reduction of selenoprotein expression. These results indicate that iAs exposure not only regulates the antioxidant selenoprotein but also regulates the endoplasmic reticulum-elastic associated selenoproteins. However, further studies are needed to confirm that these selenoprotein regulatory genes are the genes responsible for selenium in preventing inorganic arsenic toxicity. .