A protein interaction network for the analysis of the neuronal differentiation of neural stem cells in response to titanium dioxide nanoparticles

A protein interaction network for the analysis of the neuronal differentiation of neural stem cells in response to titanium dioxide nanoparticles
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用于分析神经干细胞响应二氧化钛纳米粒子的神经元分化的蛋白质相互作用网络

DOI:
10.1016/j.biomaterials.2009.12.054
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发表时间:
2010-04-01
期刊:
影响因子:
14
通讯作者:
Wen, Tieqiao
Wen, Tieqiao
中科院分区:
工程技术1区
文献类型:
--
作者:
Liu, Xiaoyan;Ren, Xiufang;Wen, Tieqiao

文献摘要

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报道了二氧化钛(TiO 2)纳米颗粒(NPs)对神经干细胞分化的影响。我们的研究结果表明,二氧化钛纳米粒子导致神经干细胞向神经元分化的趋势,表明二氧化钛纳米粒子可能是一个有益的诱导神经元分化。为了深入了解神经元分化的可能分子机制,我们进行了蛋白质-蛋白质相互作用网络(PIN)分析。为此,首先通过二维电泳分析对由TiO 2 NPs诱导的靶蛋白进行全局映射。结果表明,9个蛋白质发生了显著变化,然后对它们进行了质谱分析。所有9个蛋白质都与信号、分子伴侣、细胞骨架和核蛋白有关。进一步,基于我们的实验数据和DIP,IntAct-EBI,GRID数据库,构建了一个蛋白质-蛋白质相互作用网络,该网络提供了高度集成的蛋白质-蛋白质相互作用信息。通过对基因表达的分析,证实了涉及Cx43磷酸化的信号通路,该信号通路受蛋白激酶C β(PKC β)负调控。推测PKCE在神经干细胞的神经元分化中起关键的负作用,以响应TiO 2 NPs暴露。(C)2009爱思唯尔有限公司保留所有权利。
The effects of titanium dioxide (TiO2) nanoparticles (NPs) on the differentiation of neural stem cells are reported. Our findings indicate that TiO2 NPs lead to a differentiational tendency towards neurons from neural stem cells, suggesting TiO2 NPs might be a beneficial inducer for neuronal differentiation. To insight into the possible molecular mechanism of the neuronal differentiation, we conducted a protein-protein interaction network (PIN) analysis. To this end, a global mapping of target proteins induced by TiO2 NPs was first made by a 2-dimensional electrophoresis analysis. Results showed that 9 proteins were significantly changed and then they were subjected to the mass spectrometric assay. All 9 identified proteins are involved in signal, molecular chaperones, cytoskeleton, and nucleoprotein. Further, based on our experimental data and DIP, IntAct-EBI, GRID database, a protein-protein interaction network was constructed, which provides highly integrated information exhibiting the protein-protein interaction. By analysis of the gene expression, the signal pathway involving Cx43 phosphotylation, which is negatively regulated by the protein kinase C epsilon (PKC epsilon), is demonstrated. It is inferred that PKCE plays a pivotal negative role in the neuronal differentiation of stem neural cells in response to the TiO2 NPs exposure. (C) 2009 Elsevier Ltd. All rights reserved.