Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc
Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc
复制标题
DOI：
10.1016/j.neuint.2014.05.013
复制
发表时间：
2014-09-01
影响因子：
4.2
通讯作者：
Varea, Emilio
中科院分区：
文献类型：
--
作者：
Ballestin, Raul;Miguel Blasco-Ibanez, Jose;Varea, Emilio
锌是一种必需的微量元素，对大量结构蛋白、酶促过程和转录因子至关重要。在大脑中，锌离子参与突触传递。锌的稳态对于细胞存活和功能至关重要，并且细胞已经开发了各种各样的系统来控制锌浓度。游离锌浓度的改变与脑功能障碍有关。唐氏综合征个体存在游离锌浓度和一些与锌稳态相关的蛋白质的改变。我们已经分析了游离锌和锌螯合蛋白金属硫蛋白3在星形胶质细胞使用原代培养的小鼠模型Ts 65 Dn的量。我们已经观察到，相对于对照星形胶质细胞，三体星形胶质细胞的细胞质中的锌阳性斑点的数量更高，但是总细胞内游离锌浓度（包括斑点）的总浓度降低。使用FM 1 -43染色，我们发现内吞功能保持不变。因此，这种较低浓度的游离锌的可能解释可能是三体星形胶质细胞的细胞质中存在较高浓度的金属硫蛋白3。金属硫蛋白3的表达，使用特定的siRNA的封锁诱导游离锌的浓度在基础条件下的增加，但未能增加锌的吸收后，与锌离子孵育。(C)2014爱思唯尔有限公司版权所有。
Zinc is an essential trace element that is critical for a large number of structural proteins, enzymatic processes and transcription factors. In the brain, zinc ions are involved in synaptic transmission. The homeostasis of zinc is crucial for cell survival and function, and cells have developed a wide variety of systems to control zinc concentration. Alterations in free zinc concentration have been related with brain dysfunction. Down Syndrome individuals present alterations in free zinc concentration and in some of the proteins related with zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating protein metallothionein 3 in the astrocytes using primary cultures of the murine model Ts65Dn. We have observed a higher number of zinc positive spots in the cytoplasm of trisomic astrocytes but a decrease in the total concentration of total intracellular free zinc concentration (including the spots) respect to control astrocytes. Using FM1-43 staining, we found that the endocytic function remains unaltered. Therefore, a possible explanation for this lower concentration of free zinc could be the higher concentration of metallothionein 3 present in the cytoplasm of trisomic astrocytes. The blockade of metallothionein 3 expression using an specific siRNA induced an increase in the concentration of free zinc in basal conditions but failed to increase the uptake of zinc after incubation with zinc ions. (C) 2014 Elsevier Ltd. All rights reserved.