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Selenium regulation of selenoprotein enzyme activity and transcripts in a pilot study with Founder strains from the Collaborative Cross
PLOS ONE ( IF 2.9 ) Pub Date : 2018-01-16 , DOI: 10.1371/journal.pone.0191449
Roger A. Sunde

Rodents and humans have 24–25 selenoproteins, and these proteins contain the 21st amino acid, selenocysteine, incorporated co-translationally into the peptide backbone in a series of reactions dependent on at least 6 unique gene products. In selenium (Se) deficiency, there is differential regulation of selenoprotein expression, whereby levels of some selenoproteins and their transcripts decrease dramatically in Se deficiency, but other selenoprotein transcripts are spared this decrease; the underlying mechanism, however, is not fully understood. To begin explore the genetic basis for this variation in regulation by Se status in a pilot study, we fed Se-deficient or Se-adequate diets (0.005 or 0.2 μg Se/g, respectively) for eight weeks to the eight Founder strains of the Collaborative Cross. We found rather uniform expression of selenoenzyme activity for glutathione peroxidase (Gpx) 3 in plasma, Gpx1 in red blood cells, and Gpx1, Gpx4, and thioredoxin reductase in liver. In Founder mice, Se deficiency decreased each of these activities to a similar extent. Regulation of selenoprotein transcript expression by Se status was also globally retained intact, with dramatic down-regulation of Gpx1, Selenow, and Selenoh transcripts in all 8 strains of Founder mice. These results indicate that differential regulation of selenoprotein expression by Se status is an essential aspect of Se metabolism and selenoprotein function. A few lone differences in Se regulation were observed for individual selenoproteins in this pilot study, but these differences did not single-out one strain or one selenoprotein that consistently had unique Se regulation of selenoprotein expression. These differences should be affirmed in larger studies; use of the Diversity Outbred and Collaborative Cross strains may help to better define the functions of these selenoproteins.



中文翻译:

硒对硒蛋白的酶活性和转录物的调节作用

啮齿动物和人类有24-25硒蛋白,这些蛋白含有21氨基酸,硒代半胱氨酸,在至少依赖于6种独特基因产物的一系列反应中,共翻译地掺入肽主链。在硒缺乏症中,硒蛋白表达存在差异性调节,硒缺乏症中某些硒蛋白及其转录物水平显着下降,但其他硒蛋白转录物可避免这种下降。但是,尚未完全理解其基本机制。为了在一项前期研究中开始探索这种通过硒状态进行调控的遗传基础,我们将低硒或低硒饮食(分别为0.005或0.2μgSe / g)喂食了8种Founder菌株,持续了八周。协作十字架。我们发现血浆中的谷胱甘肽过氧化物酶(Gpx)3,红细胞中的Gpx1的硒酶活性相当均匀地表达,肝脏中的Gpx1,Gpx4和硫氧还蛋白还原酶。在Founder小鼠中,硒缺乏会以类似的程度降低这些活动中的每一种。硒状态对硒蛋白转录物表达的调节也保持了完整,并显着下调了硒的表达。Founder小鼠的所有8个品系中的Gpx1SelenowSelenoh转录本。这些结果表明,硒状态对硒蛋白表达的差异调节是硒代谢和硒蛋白功能的重要方面。在这项先导研究中,观察到个别硒蛋白的硒调节存在一些单独的差异,但这些差异并未选择出一株或一种硒蛋白始终具有独特硒调节蛋白表达的硒蛋白。这些差异应在较大的研究中予以确认;使用多样性近交和协作交叉菌株可能有助于更好地定义这些硒蛋白的功能。

更新日期:2018-01-17
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