Comparison of different selenocompounds with respect to nutritional value vs. toxicity using liver cells in culture
Comparison of different selenocompounds with respect to nutritional value vs. toxicity using liver cells in culture
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DOI：
10.1016/j.jnutbio.2010.08.006
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发表时间：
2011-10-01
影响因子：
5.6
通讯作者：
Schomburg, Lutz
中科院分区：
文献类型：
--
作者：
Hoefig, Carolin S.;Renko, Kostja;Schomburg, Lutz
人体必需微量元素硒主要通过酶促活性硒蛋白发挥其生物学效应。它们的生物合成取决于第21蛋白氨基酸硒代半胱氨酸，因此对膳食硒供应。肝源性硒蛋白P（SEPP）是血液中控制硒转运和分布的中心硒蛋白。肾源性细胞外谷胱甘肽过氧化物酶是另一个相关的血清硒蛋白，依赖于SEPP的生物合成。因此，分泌SEPP的肝细胞是至关重要的营养来源转化为血清硒，支持硒的地位和硒蛋白的生物合成在其他tissues.In比较的生物活性的10种不同的硒化合物，其剂量依赖性的毒性和营养品质，以支持SEPP和谷胱甘肽过氧化物酶的生物合成测定在小鼠和两个人的肝细胞系。观察到对活力和SEPP生产的特征剂量和时间依赖性影响。与100 nM亚硒酸钠、L-或DL-硒代半胱氨酸、硒代二谷胱甘肽或硒甲基-硒代半胱氨酸一起孵育72小时后，培养基中的SEPP浓度增加至对照的6.5倍。相比之下，硒酸钠、L-或DL-硒代甲硫氨酸或甲基亚硒酸在这些条件下效果较差，并使SEPP增加2.5倍。正如预期的那样，依布硒啉没有增加硒蛋白的产生，支持其作为稳定的硒化合物的分类。Methylseleninic acid，L-selenocystine，selenodigluoride或亚硒酸盐诱导细胞死亡的微摩尔浓度，而selenomethioride或ebselen是没有毒性的浓度范围内tested.Our结果表明，肝硒蛋白的生产和毒性的selenocomposites不相关，而是代表化合物的特定属性。硒甲基硒代半胱氨酸的有利特性保证了其作为补充目的的有希望的选择的考虑。(C)2011 Elsevier Inc. All rights reserved.
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. (C) 2011 Elsevier Inc. All rights reserved.