Liu Fu, Gao Mei-Ling, Bai Juan, Wang Ya-Fang, Li Xia-Qing
Department of Pathophysiology, Shanxi Medical University, Taiyuan, Shanxi Province, China.
Department of Pathophysiology, Shanxi Medical University, Taiyuan, Shanxi Province; Department of Vascular Surgery, People's Hospital of Gansu Province, Lanzhou, Gansu Province, China.
Neural Regen Res. 2018 Nov;13(11):1893-1899. doi: 10.4103/1673-5374.239438.
Myelin-associated glycoprotein (MAG) inhibits the growth of neurites from nerve cells. Extraction and purification of MAG require complex operations; therefore, we attempted to determine whether commercially available MAG-Fc can replace endogenous MAG for research purposes. Immunofluorescence using specific antibodies against MAG, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB) was used to determine whether MAG-Fc can be endocytosed by neuro-2a cells. In addition, neurite outgrowth of neuro-2a cells treated with different doses of MAG-Fc was evaluated. Enzyme linked immunosorbent assays were used to measure RhoA activity. Western blot assays were conducted to assess Rho-associated protein kinase (ROCK) phosphorylation. Neuro-2a cells expressed NgR and PirB, and MAG-Fc could be endocytosed by binding to NgR and PirB. This activated intracellular signaling pathways to increase RhoA activity and ROCK phosphorylation, ultimately inhibiting neurite outgrowth. These findings not only verify that MAG-Fc can inhibit the growth of neural neurites by activating RhoA signaling pathways, similarly to endogenous MAG, but also clearly demonstrate that commercial MAG-Fc is suitable for experimental studies of neurite outgrowth.
髓鞘相关糖蛋白(MAG)可抑制神经细胞轴突的生长。MAG的提取和纯化需要复杂的操作;因此,我们试图确定市售的MAG-Fc是否可以替代内源性MAG用于研究目的。使用针对MAG、Nogo受体(NgR)和配对免疫球蛋白样受体B(PirB)的特异性抗体进行免疫荧光检测,以确定MAG-Fc是否能被神经2a细胞内吞。此外,还评估了用不同剂量的MAG-Fc处理的神经2a细胞的轴突生长情况。采用酶联免疫吸附测定法测量RhoA活性。进行蛋白质免疫印迹分析以评估Rho相关蛋白激酶(ROCK)的磷酸化情况。神经2a细胞表达NgR和PirB,MAG-Fc可通过与NgR和PirB结合而被内吞。这激活了细胞内信号通路,增加了RhoA活性和ROCK磷酸化,最终抑制了轴突生长。这些发现不仅证实了MAG-Fc与内源性MAG一样,可通过激活RhoA信号通路抑制神经轴突的生长,还清楚地表明市售的MAG-Fc适用于轴突生长的实验研究。