Peptidyl-prolyl cis-trans isomerase A participates in the selenium transport into the rat brain
Peptidyl-prolyl cis-trans isomerase A participates in the selenium transport into the rat brain
复制标题
肽基脯氨酰顺反异构酶 A 参与硒转运至大鼠脑中
DOI：
10.1007/s00775-021-01903-6
复制
发表时间：
2021
影响因子：
3
通讯作者：
M. Nakayama
中科院分区：
文献类型：
--
作者：
1.S. Yoshida;A. Yamamoto;H. Masumoto;T. Fuchigami;A. Toriba;M. Haratake;M. Nakayama
硒是一种必需的微量营养素，在大脑中起着重要作用。硒蛋白P（Selenoprotein P，SELENOP）是血浆中一种主要的硒蛋白，被认为是将硒转运到大脑的主要途径。然而，硒敲除小鼠喂养的饮食含有足够量的硒显示没有客观的神经功能障碍，在硒缺乏的饮食喂养硒敲除小鼠观察。这一事实表明，来自低质量硒源化合物的硒可以通过不依赖于硒的替代途径转运到大脑。在这项研究中，为了获得关于非依赖于硒的转运途径的基本信息，我们进行了离体实验，其中分析了大鼠脑细胞膜组分，使用其反应性代谢中间体硒三硫化物（STS）和MALDI TOF-质谱法寻找硒结合和/或相互作用蛋白。发现几种具有半胱氨酸（C）巯基的膜蛋白通过巯基交换反应与STS反应。从胰蛋白酶片段化实验和数据库检索中，脑细胞膜组分中的一种含C蛋白被鉴定为肽基-脯氨酰顺式-transisomerase（PPIase）A。在大鼠PPIase A的4个C残基中，通过使用C突变的重组蛋白的评估，证明21st C与STS反应。PPIase A广泛表达，并与多种生物学重要事件相关，如免疫调节、细胞内信号传导、转录调节和蛋白质运输。因此，PPIase A被认为参与了硒向大鼠大脑的转运。
Selenium, an essential micronutrient, plays vital roles in the brain. Selenoprotein P (SELENOP), a major plasma selenoprotein, is thought to transport selenium to the brain. However,Selenop-knockout mice fed a diet containing an adequate amount of selenium shows no objective neurological dysfunction which is observed in the selenium-deficient diet-fedSelenop-knockout mice. This fact indicated that selenium from low-mass selenium-source compounds can be transported by SELENOP-independent alternative pathways to the brain. In this study, to obtain the basic information about the SELENOP-independent transport pathways, we performed ex vivo experiments in which the rat brain cell membrane fraction was analyzed to find selenium-binding and/or -interactive proteins using its reactive metabolic intermediate, selenotrisulfide (STS), and MALDI TOF-mass spectrometry. Several membrane proteins with the cysteine (C) thiol were found to be reactive with STS through the thiol-exchange reaction. One of the C-containing proteins in the brain cell membrane fraction was identified as peptidyl-prolylcis–transisomerase (PPIase) A from tryptic fragmentation experiments and database search. Among the 4 C residues in rat PPIase A, 21st C was proved to react with STS by assessment using C mutated recombinant proteins. PPIase A is ubiquitously expressed and also associates with a variety of biologically important events such as immunomodulation, intracellular signaling, transcriptional regulation and protein trafficking. Consequently, PPIase A was thought to participate in the selenium transport into the rat brain.Graphic abstract