Selenoprotein SELENOK Enhances the Migration and Phagocytosis of Microglial Cells by Increasing the Cytosolic Free Ca2+ Level Resulted from the Up-Regulation of IP3R
Selenoprotein SELENOK Enhances the Migration and Phagocytosis of Microglial Cells by Increasing the Cytosolic Free Ca2+ Level Resulted from the Up-Regulation of IP3R
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DOI：
10.1016/j.neuroscience.2019.02.029
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发表时间：
2019-05-15
期刊：
影响因子：
3.3
通讯作者：
Lu, Jing
中科院分区：
文献类型：
--
作者：
Meng, Xue-Lian;Chen, Chang-Lan;Lu, Jing
增强小胶质细胞的迁移和吞噬功能对于降低阿尔茨海默病（Alzheimer's disease，AD）和帕金森病（Parkinson's disease，PD）等神经退行性疾病的发病风险具有重要意义。研究了小鼠硒蛋白K（mSELENOK）对BV 2小胶质细胞迁移和吞噬功能的影响及其机制。结果表明，过表达mSELENOK可增强小胶质细胞的迁移和吞噬能力，而敲低mSELENOK则可降低细胞的迁移和吞噬能力。由于mSELENOK在小胶质细胞中的过表达，细胞溶质游离Ca 2+水平和三磷酸肌醇受体（IP 3R）mRNA转录和蛋白表达也显著增加。与此相反，mSELENOK基因敲除细胞内游离Ca ~（2+）水平、IP 3R mRNA转录和蛋白表达均显著降低。2-IP 3R拮抗剂2-APB可抑制mSELENOK过表达的小胶质细胞的迁移、吞噬和胞浆游离Ca 2+水平的升高，IP 3R 3敲低可抑制mSELENOK过表达的小胶质细胞胞浆Ca 2+水平的升高。进一步的研究表明，硒补充剂（Na 2SeO 3）可以显著增加mSELENOK在小胶质细胞中的表达。综上所述，这些数据表明mSELENOK可以通过上调IP 3R的表达来增加小胶质细胞的胞浆游离Ca 2+水平，从而增强小胶质细胞的迁移和吞噬作用。我们的研究结果表明，mSELENOK是一种重要的硒蛋白，它在微量元素硒的功能中发挥作用，并能增强小胶质细胞的迁移和吞噬功能。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Enhancing the migration and phagocytosis of microglial cells is of great significance for the reducing of the risk of the neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The effect of mouse selenoprotein K (mSELENOK) on the migration and phagocytosis of BV2 microglial cells and its mechanism were studied. The results showed that the over-expression of mSELENOK can increase the migratory and phagocytic abilities of the microglial cells, while the knockdown of mSELENOK can decrease the migratory and phagocytic abilities of the cells. The cytosolic free Ca2+ level and inositol trisphosphate receptor (IP3R) mRNA transcript and protein expression were also increased significantly as the consequence of the over-expression of mSELENOK in the microglial cells. On the contrary, the level of cytosolic free Ca2+ and the mRNA transcript and protein expression of IP3R in mSELENOK knockdown cells were decreased significantly. 2-aminoethoxydiphenyl borate (2-APB), an antagonist of IP3R, could prevent the increased migration, phagocytosis, and cytosolic free Ca2+ level of mSELENOK over-expressed microglial cells, and knockdown of IP3R3 could reduce the increased cytosolic Ca2+ level in mSELENOK over-expressed microglial cells. Further studies revealed that selenium supplement (Na2SeO3) can increase the expression of mSELENOK in microglial cells significantly. In summary, these data suggest that mSELENOK can increase cytosolic free Ca2+ level of microglial cells by up-regulating the expression of IP3R, thus enhancing the migration and phagocytosis of microglial cells. Our results indicated that mSELENOK is an important selenoprotein, which plays a role in trace element selenium's functions and can enhance the migration and phagocytosis of microglial cells. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.