Effects of arsenite in astrocytes on neuronal signaling transduction
Effects of arsenite in astrocytes on neuronal signaling transduction
复制标题
星形胶质细胞中亚砷酸盐对神经信号转导的影响
DOI：
10.1016/j.tox.2012.10.024
复制
发表时间：
2013-01-07
期刊：
影响因子：
4.5
通讯作者：
Sun, Guifan
中科院分区：
文献类型：
--
作者：
Wang, Yan;Zhao, Fenghong;Sun, Guifan
本研究的主要目的是检验砷通过影响星形胶质细胞而引起神经毒性的假设。将星形胶质细胞分别暴露于0、5或10 μ M的亚砷酸溶液中24 h，然后与新鲜培养液孵育6 h后收集星形胶质细胞条件培养液（ACM）。原代培养的神经元分为4组，即未接触ACM的神经元（I组）和接触0、5或10 μ M亚砷酸盐处理的星形胶质细胞的ACM的神经元（II-IV组）。用ACM孵育神经元4、8和12 h后，测定N-甲基-D-天冬氨酸受体（NR 1、NR 2A、NR 2B）、钙调素依赖性蛋白激酶（CaMK Ⅱ）和腺苷酸环化酶（AC）的蛋白表达。与ACM孵育72 h后，观察形态学变化和突触形成。与Ⅱ组相比，Ⅲ组和Ⅳ组突触形成及NR 2A、NR 2B、CaMK Ⅱ和AC蛋白表达均受到明显抑制。此外，与I组相比，II组的突触形成和CaMK II和AC的蛋白表达显著增强。总之，这项研究的结果表明，砷在星形胶质细胞可能会损害突触的形成，通过干扰星形胶质细胞对神经元信号转导的影响。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
The main purpose of this study was to test the hypothesis that arsenite induces neurotoxicity via effects on astrocytes. Astrocytes were exposed to 0, 5 or 10 p,M arsenite in medium for 24 h, and then astrocyte-conditioned medium (ACM) was collected after incubation with fresh medium for 6 h. Primary neuron cultures were divided into four groups due to ACM, which were neurons without ACM exposure (group I) and neurons exposed to ACM from 0, 5 or 10 p,M arsenite treated astrocytes (group II-IV). Protein expression of N-methyl-D-aspartate receptors (NR1, NR2A, NR2B), calmodulin-dependent protein kinasell (CaMKII) and adenylate cyclase (AC) in neurons were measured after incubation with ACM for 4, 8 or 12 h. Morphological changes and synaptic formation were observed after a 72 h-incubation with ACM. Compared to group II, synaptic formation and protein expression of NR2A, NR2B, CaMKII and AC in group III and IV were significantly suppressed. Moreover, synaptic formation and protein expression of CaMKII and AC in group II were significantly enhanced when compared with group I. Taken together, findings from this study suggested that arsenic in astrocytes might impair synaptic formation through disturbing astrocytic effects on neuronal signal transduction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.