Segawa Shohei, Tatsumi Nao, Ohishi Akihiro, Nishida Kentaro, Nagasawa Kazuki
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Metallomics. 2015 Jul;7(7):1067-77. doi: 10.1039/c5mt00085h.
To elucidate the regulatory mechanism for extracellular zinc in the CNS, we examined the zinc uptake characteristics in mouse astrocytes and microglia. Zinc was taken up into the two cell types time-dependently, and the cell-to-medium concentration (C/M) ratio in the initial uptake phase in astrocytes was significantly smaller than that in microglia, while in the steady state phase, there was no difference in their C/M ratios. In both astrocytes and microglia, the zinc uptake was mediated, at least in part, by high- and low-affinity systems. There were no differences for both in the Km values for zinc uptake between astrocytes and microglia, and those for the low-affinity system in both cell types were the same as that for mouse ZIP1 reported previously. On the other hand, the Vmax values for both systems were greater in microglia than in astrocytes. Among ZIP isoforms, expression of ZIP1 was high in astrocytes and microglia. Nickel, a competitive inhibitor of ZIP1, and ZIP1 knock-down decreased zinc uptake by both types of cells. Overall, it is demonstrated that astrocytes and microglia had a similar uptake system for zinc including ZIP1, and the differences found in their uptake profiles imply that they play different roles in the regulation of extracellular zinc to maintain brain homeostasis.
为阐明中枢神经系统中细胞外锌的调节机制，我们研究了小鼠星形胶质细胞和小胶质细胞对锌的摄取特性。锌以时间依赖性方式被摄取到这两种细胞类型中，星形胶质细胞初始摄取阶段的细胞与培养基浓度（C/M）比显著低于小胶质细胞，而在稳态阶段，它们的C/M比没有差异。在星形胶质细胞和小胶质细胞中，锌摄取至少部分由高亲和力和低亲和力系统介导。星形胶质细胞和小胶质细胞对锌摄取的Km值没有差异，且两种细胞类型中低亲和力系统的Km值与先前报道的小鼠ZIP1相同。另一方面，小胶质细胞中两种系统的Vmax值均高于星形胶质细胞。在ZIP亚型中，ZIP1在星形胶质细胞和小胶质细胞中表达较高。ZIP1的竞争性抑制剂镍和ZIP1基因敲低均降低了两种细胞类型对锌的摄取。总体而言，结果表明星形胶质细胞和小胶质细胞具有相似的包括ZIP1在内的锌摄取系统，它们摄取特征的差异表明它们在调节细胞外锌以维持脑内稳态中发挥不同作用。
