School of Pharmaceutical Science, Liaoning University, Shenyang, China; Research Center for Natural product pharmacy of Liaoning Province, Shenyang, China.
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Research Center for Natural product pharmacy of Liaoning Province, Shenyang, China.
Neuroscience. 2019 May 15;406:38-49. doi: 10.1016/j.neuroscience.2019.02.029. Epub 2019 Mar 5.
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 Ca level and inositol trisphosphate receptor (IPR) 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 Ca and the mRNA transcript and protein expression of IPR in mSELENOK knockdown cells were decreased significantly. 2-aminoethoxydiphenyl borate (2-APB), an antagonist of IPR, could prevent the increased migration, phagocytosis, and cytosolic free Ca level of mSELENOK over-expressed microglial cells, and knockdown of IPR could reduce the increased cytosolic Ca level in mSELENOK over-expressed microglial cells. Further studies revealed that selenium supplement (NaSeO) can increase the expression of mSELENOK in microglial cells significantly. In summary, these data suggest that mSELENOK can increase cytosolic free Ca level of microglial cells by up-regulating the expression of IPR, 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.
增强小胶质细胞的迁移和吞噬作用对于降低神经退行性疾病（如阿尔茨海默病（AD）和帕金森病（PD））的风险具有重要意义。本研究探讨了小鼠硒蛋白 K（mSELENOK）对 BV2 小胶质细胞迁移和吞噬作用的影响及其机制。结果表明，mSELENOK 的过表达可增强小胶质细胞的迁移和吞噬能力，而 mSELENOK 的敲低则降低了细胞的迁移和吞噬能力。此外，mSELENOK 过表达可使细胞内游离钙水平和肌醇三磷酸受体（IPR）mRNA 转录本和蛋白表达显著增加。相反，mSELENOK 敲低细胞内游离钙水平和 IPR 的 mRNA 转录本和蛋白表达均显著降低。IPR 的拮抗剂 2-APB 可阻止 mSELENOK 过表达引起的小胶质细胞迁移、吞噬和细胞内游离钙水平的增加，而 IPR 的敲低则降低了 mSELENOK 过表达引起的细胞内游离钙水平的增加。进一步的研究表明，硒补充剂（NaSeO）可显著增加小胶质细胞中 mSELENOK 的表达。综上所述，这些数据表明，mSELENOK 通过上调 IPR 的表达来增加小胶质细胞内的游离钙水平，从而增强小胶质细胞的迁移和吞噬作用。我们的结果表明，mSELENOK 是一种重要的硒蛋白，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作用。
