Ion-shedding zinc oxide nanoparticles induce microglial BV2 cell proliferation via the ERK and Akt signaling pathways

Given the wide application of zinc oxide nanoparticles (ZnO NPs), the health hazards of these particles have attracted extensive worldwide attention. Many more studies on the biological interactions of ZnO NPs have been performed in recent years. In this study, we focused on the biological effects on BV2 microglial cells induced by ZnO NPs at non- or sub-toxic concentrations. We found that ZnO NPs at a concentration of 5 μg/ml could significantly activate cell proliferation, while ZnO NPs at other concentrations did not. We also found that ZnO NPs induced microglial cell activation in a time-dependent manner. Moreover, a potent increase in the ratio of cells in S phase at all ZnO NPs concentrations was observed in a cell cycle analysis. Using inductively coupled plasma mass spectrometry (ICP-MS) and immunocytochemistry techniques, we demonstrated that ZnO dissolution could occur in the culture medium and in the lysosomes of BV2 cells. ZnO NPs significantly induced the phosphorylation of ERK and Akt, which might be involved in promoting cell proliferation. In conclusion, our results demonstrated that ZnO NPs induced BV2 microglial cell proliferation probably via the release of zinc ions from ZnO, which could then activate the ERK and Akt signaling pathways.