Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells
Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells
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乙酰胆碱酯酶是 GFAP 表达的调节剂，也是敌敌畏在大鼠胶质瘤 C6 细胞星形胶质细胞分化中的靶标
DOI：
10.1016/j.brainres.2013.08.031
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发表时间：
2013
期刊：
影响因子：
2.9
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Ozawa;A.;Kadowaki;E.;Haga;Y.;Sekiguchi;H.;Hemmi;N.;Kaneko;T.;Maki;T.;Sakabe;K.;Hara;S.;Yamamoto;M.;Arishima;K.;Sakaue;M.
神经毒素的主要目标是神经元，因为它们构成神经功能的主要部分，但神经胶质细胞可能是间接目标，因为它们支持神经元的功能。在神经胶质细胞中，星形胶质细胞尤其充当“护士细胞”，调节神经元的存活和功能。在本研究中，为了揭示已知的神经毒性物质有机磷敌敌畏 (DDVP) 是否影响星形胶质细胞的分化，我们在大鼠胶质瘤 C6 细胞中使用了星形胶质细胞分化模型。 DDVP 处理抑制了分化 C6 细胞的形态变化和 GFAP 表达的诱导。 DDVP 已知的潜在靶标是乙酰胆碱酯酶 (AChE)、脂肪酸酰胺水解酶和甲基鸟嘌呤甲基转移酶。在针对这些酶的特异性抑制剂中，AChE 抑制剂 paraoxon 成功抑制了分化 C6 细胞中的细胞形态变化和 GFAP 表达的诱导。这些结果表明，DDVP 抑制 C6 星形胶质细胞分化模型中的分化，其中至少涉及 AChE 抑制，并且 AChE 是分化的有效调节剂。此外，考虑到AChE的主要底物是ACh，因此ACh可能充当星形胶质细胞分化的调节因子。
The main target of neurotoxins is neurons because they comprise the main part of neural function, but glial cells may be indirect targets because they support the function of neurons. Among the glial cells, astrocytes in particular act as “nurse cells”, regulating neuronal survival and functions. In the present study, to reveal whether a known neurotoxic substance, organophosphate dichlorvos (DDVP), affects the differentiation of astrocytes, we used an astrocyte differentiation model in rat glioma C6 cells. Morphological change and induction of GFAP expression in the differentiating C6 cells were suppressed by DDVP treatment. The known potential targets of DDVP are acetylcholine esterase (AChE), fatty acid amide hydrolase and methyl guanine methyl transferase. Among the specific inhibitors against these enzymes, the AChE inhibitor paraoxon successfully suppressed the cellular morphological changes and the induction of GFAP expression in differentiating C6 cells. These results indicate that DDVP inhibits differentiation in the C6 astrocyte-differentiation model, in which at least AChE inhibition is involved and that AChE is a potent regulator of the differentiation. Furthermore, considering that the main substrate of AChE is ACh, thus, ACh may act as regulators of astrocyte differentiation.