Deletion of selenoprotein P upregulates urinary selenium excretion and depresses whole-body selenium content
Deletion of selenoprotein P upregulates urinary selenium excretion and depresses whole-body selenium content
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DOI：
10.1016/j.bbagen.2006.08.010
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发表时间：
2006-12-01
影响因子：
3
通讯作者：
Norsworthy, Brooke K.
中科院分区：
文献类型：
--
作者：
Burk, Raymond F.;Hill, Kristina E.;Norsworthy, Brooke K.
小鼠硒蛋白P基因（Sepp 1）的缺失降低了许多组织中的硒浓度。我们检查了Sepp 1（-/-）和Sepp 1（+/+）小鼠的硒稳态，以评估其机制。肝脏产生并输出硒蛋白P，其将硒转运到外周组织，以及尿硒代谢物，其调节全身硒。在接近营养需求的硒摄入量下，Sepp 1（-/-）小鼠的全身硒浓度为Sepp 1（+/+）小鼠的72%至75%。基因型不影响硒的膳食摄入量。Sepp 1（-/-）小鼠尿液中排出的硒相对于其全身硒大约是Sepp 1（+/+）小鼠的1.5倍。此外，Sepp 1（-/-）小鼠灌胃Se-75（3）2-后，尿中Se-75的排泄量是Sepp 1（+/+）小鼠的1.7至2.4倍。这些结果表明，硒蛋白P的缺失增加尿中硒的排泄。当尿中小分子Se-75静脉注射到小鼠体内时，超过90%的Se-75在24 h内出现在尿中，无论硒状态如何。这表明尿硒主要用于排泄，而不是被组织利用。我们的研究结果表明，硒蛋白P的缺失导致尿硒排泄增加。我们认为，在肝脏中硒蛋白P合成的情况下，使更多的硒可用于尿代谢产物的合成，增加硒从生物体的损失，并导致全身硒的减少和Sepp 1（-/-）小鼠的组织中观察到的一些减少。(c)2006 Elsevier B. V.保留所有权利。
Deletion of the mouse selenoprotein P gene (Sepp1) lowers selenium concentrations in many tissues. We examined selenium homeostasis in Sepp1(-/-) and Sepp1(+/+) mice to assess the mechanism of this. The liver produces and exports selenoprotein P, which transports selenium to peripheral tissues, and urinary selenium metabolites, which regulate whole-body selenium. At intakes of selenium near the nutritional requirement, Sepp1(-/-) mice had whole-body selenium concentrations 72 to 75% of Sepp1(+/+) mice. Genotype did not affect dietary intake of selenium. Sepp1(-/-) mice excreted in their urine approximately 1.5 times more selenium in relation to their whole-body selenium than did Sepp1(+/+) mice. In addition, Sepp1(-/-) mice gavaged with Se-75(3)2- excreted 1.7 to 2.4 times as much of the Se-75 in the urine as did Sepp1(+/+) mice. These findings demonstrate that deletion of selenoprotein P raises urinary excretion of selenium. When urinary small-molecule Se-75 was injected intravenously into mice, over 90% of the Se-75 appeared in the urine within 24 h, regardless of selenium status. This shows that urinary selenium is dedicated to excretion and not to utilization by tissues. Our results indicate that deletion of selenoprotein P leads to increased urinary selenium excretion. We propose that the absence of selenoprotein P synthesis in the liver makes more selenium available for urinary metabolite synthesis, increasing loss of selenium from the organism and causing the decrease in whole-body selenium and some of the decreases observed in tissues of Sepp1(-/-) mice. (c) 2006 Elsevier B.V. All rights reserved.