Dietary selenium deficiency or selenomethionine excess drastically alters organ selenium contents without altering the expression of most selenoproteins in mice
Dietary selenium deficiency or selenomethionine excess drastically alters organ selenium contents without altering the expression of most selenoproteins in mice
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DOI：
10.1016/j.jnutbio.2019.03.020
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Ishii, Isao
中科院分区：
文献类型：
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作者：
Akahoshi, Noriyuki;Anan, Yasumi;Ishii, Isao
硒是一种必需的微量元素，缺乏硒会导致心肌病、心律失常和感染易感性增加。此类临床症状被认为主要归因于人类中 25 种含硒半胱氨酸的硒蛋白中的一些表达降低。相反，硒过量的饮食会导致急性中毒和慢性症状，其机制尚不清楚。为了揭示体内硒缺乏和过量对硒蛋白表达的影响，小鼠（拥有 24 种硒蛋白）被喂食缺硒或硒代蛋氨酸过量饮食长达 4 周，并测量九种代表性硒蛋白的表达水平 [谷胱甘肽过氧化物酶 (Gpx) 1/2/3/4、硫氧还蛋白还原酶 1/2、 在 10 个器官（脑、心、肝、肺、肾、胰腺、脾、睾丸、骨骼肌和胸腺）中测量了脱碘酶 1 和硒蛋白 P/S]。我们观察到缺硒小鼠大多数器官（睾丸除外）的硒含量随时间呈依赖性下降，但九种硒蛋白的表达水平却没有下降，但心脏/肝脏/肾脏/胰腺/脾脏中的Gpx1/2和胰腺/脾脏中的Gpx3除外。由于 Gpx3（一种血浆型 Gpx）的表达/活性降低，血清脂质过氧化水平因硒缺乏而上调。相比之下，在硒代蛋氨酸过量的小鼠中，所有器官的硒含量都观察到了时间依赖性的增加，但大多数器官中九种硒蛋白的表达水平没有观察到。然而，在肝脏/肾脏中观察到蛋白质结合硒水平显着升高。这些结果表明，对硒缺乏和硒代蛋氨酸过量的全身反应分别涉及一些含硒蛋白（例如 Gpx1/Gpx3）的下调和含硒蛋白（非硒蛋白）的上调。 (C) 2019 Elsevier Inc. 保留所有权利。
Selenium is an essential trace element, and its deficiency can cause cardiomyopathy, arrhythmias and increased susceptibility to infection. Such clinical symptoms are considered primarily attributed to decreased expression of some of the 25 selenocysteine-containing selenoproteins in humans. Conversely, a selenium-excessive diet can cause acute poisoning and chronic symptoms with unknown mechanisms. To reveal the impact of selenium deficiency and excess on selenoprotein expression in vivo, mice (that possess 24 selenoproteins) were fed with selenium-deficient or selenomethionine-excessive diets for up to 4 weeks, and the expression levels of nine representative selenoproteins [glutathione peroxidase (Gpx) 1/2/3/4, thioredoxin reductase 1/2, deiodinase 1, and selenoprotein P/S] were measured in 10 organs (brain, heart, liver, lung, kidney, pancreas, spleen, testis, skeletal muscle and thymus). We observed a time-dependent decrease in the selenium content of most organs (except testis) of selenium-deficient mice but not in the expression levels of the nine selenoproteins, with the exceptions of Gpx1/2 in the heart/liver/kidney/pancreas/spleen and Gpx3 in the pancreas/spleen. Serum lipid peroxidation levels were up-regulated in response to Se deficiency because of the decreased expression/activity of Gpx3, a plasma-type Gpx. In contrast, a time-dependent increase was observed in the selenium content of all organs but not the expression levels of the nine selenoproteins in most organs of selenomethionine-excessive mice; however, markedly elevated protein-bound selenium levels were observed in the liver/kidney. These results suggest that the systemic response to selenium deficiency and selenomethionine excess involves the down-regulation of some selenoproteins such as Gpx1/Gpx3 and up-regulation of selenium-containing proteins (not selenoproteins), respectively. (C) 2019 Elsevier Inc. All rights reserved.