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

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 phosphorylation, which is negatively regulated by the protein kinase C epsilon (PKCɛ), is demonstrated. It is inferred that PKCɛ plays a pivotal negative role in the neuronal differentiation of stem neural cells in response to the TiO2 NPs exposure.