Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, CVK, Südring, Berlin, Germany.
J Nutr Biochem. 2011 Oct;22(10):945-55. doi: 10.1016/j.jnutbio.2010.08.006. Epub 2010 Dec 28.
The essential micronutrient selenium (Se) exerts its biological effects mainly through enzymatically active selenoproteins. Their biosynthesis depends on the 21st proteinogenic amino acid selenocysteine and thus on dietary Se supply. Hepatically derived selenoprotein P (SEPP) is the central selenoprotein in blood controlling Se transport and distribution. Kidney-derived extracellular glutathione peroxidase is another relevant serum selenoprotein depending on SEPP for biosynthesis. Therefore, secretion of SEPP by hepatocytes is crucial to convert nutritional sources into serum Se, supporting Se status and selenoprotein biosynthesis in other tissues. In order to compare the bioactivity of 10 different selenocompounds, their dose-dependent toxicities and nutritional qualities to support SEPP and glutathione peroxidase biosynthesis were determined in a murine and two human liver cell lines. Characteristic dose- and time-dependent effects on viability and SEPP production were observed. Incubations with 100 nM sodium selenite, l- or dl-selenocystine, selenodiglutathione or selenomethyl-selenocysteine increased SEPP concentrations in the culture medium up to 6.5-fold over control after 72 h. In comparison, sodium selenate, l- or dl-selenomethionine or methylseleninic acid was less effective and increased SEPP by 2.5-fold under these conditions. As expected, ebselen did not increase selenoprotein production, supporting its classification as a stable selenocompound. Methylseleninic acid, l-selenocystine, selenodiglutathione or selenite induced cell death in micromolar concentrations, whereas selenomethionine or ebselen was not toxic within the concentration range tested. Our results indicate that hepatic selenoprotein production and toxicity of selenocompounds do not correlate with and rather represent compound-specific properties. The favourable profile of selenomethylselenocysteine warrants its consideration as a promising option for supplementation purposes.
必需微量元素硒（Se）主要通过具有酶活性的硒蛋白发挥其生物学效应。它们的生物合成依赖于第 21 种蛋白质氨基酸硒代半胱氨酸，因此依赖于膳食 Se 的供应。肝源性硒蛋白 P（SEPP）是血液中控制 Se 转运和分布的主要硒蛋白。肾源性细胞外谷胱甘肽过氧化物酶是另一种相关的血清硒蛋白，其生物合成依赖于 SEPP。因此，肝细胞分泌 SEPP 对于将营养源转化为血清 Se、维持其他组织的 Se 状态和硒蛋白生物合成至关重要。为了比较 10 种不同硒化合物的生物活性，在鼠和两种人肝细胞系中，测定了它们对 SEPP 和谷胱甘肽过氧化物酶生物合成的剂量依赖性毒性和营养质量。观察到了特征性的剂量和时间依赖性对活力和 SEPP 产生的影响。与对照相比，在 72 小时后，100 nM 亚硒酸钠、l-或 dl-硒代半胱氨酸、硒代二半胱氨酸或硒代甲基硒代半胱氨酸孵育可将培养基中 SEPP 的浓度提高 6.5 倍。相比之下，亚硒酸钠、l-或 dl-蛋氨酸或甲基亚硒酸在这些条件下将 SEPP 增加 2.5 倍。正如预期的那样，艾地苯醌不会增加硒蛋白的产生，支持其被归类为稳定的硒化合物。在微摩尔浓度下，甲基亚硒酸、l-硒代半胱氨酸、硒代二半胱氨酸或亚硒酸钠诱导细胞死亡，而蛋氨酸或艾地苯醌在测试浓度范围内没有毒性。我们的结果表明，肝硒蛋白的产生和硒化合物的毒性与化合物的特异性特性不相关，而是代表化合物的特异性特性。硒代甲基硒代半胱氨酸的良好特征使其成为补充的有希望的选择。
