TRPC6-Mediated Ca2+ Entry Essential for the Regulation of Nano-ZnO Induced Autophagy in SH-SY5Y Cells

Abstract

Recently, possible applications of zinc oxide nanoparticles (nano-ZnO) have been extensively studied owing to their ease of synthesis. However, the effect of nano-ZnO on the nervous system remains unclear. This study investigates the action of nano-ZnO on SH-SY5Y neuroblastoma cells. We found that nano-ZnO (0–50 µg/mL) induced a significant decrease in cell survival rate in a dose-dependent manner, and increased LC3 puncta formation. However, the apoptosis was not affected by nano-ZnO, because the protein levels of cytochrome c, caspase-3, Bcl-xL, and BAX were not varied by the nano-ZnO treatment. Nano-ZnO increased Ca²⁺ entry and the expression of TRPC6.The results suggested that nano-ZnO increased [Ca²⁺] through the TRPC-dependent Ca²⁺ influx, since Ca²⁺ influx can be prevented by the TRPC inhibitor. Furthermore, cells on nano-ZnO-treatment groups displayed loss of F-actin in a dose dependent manner, which also could be prevented by TRPC inhibitor. Herein, we demonstrated that the nano-ZnO activated TRPC6 channel, thereby increasing the Ca²⁺ flux and resulting in increased autophagy. Nano-ZnO could have possible anticancer effects in neuroblastoma by inhibiting the proliferation of tumor cells. However, we should also pay attention toward the biosecurity of nano materials. Graphic Abstract