The mTOR/GCLc/GSH Pathway Mediates the Dose-Dependent Bidirectional Regulation of ROS Induced by TiO₂ NPs in Neurogenic Cells

Figure 7

The mTOR/GCLc/GSH pathway mediated the dose dependently bidirectional regulation of ROS induced by TiO2 NPs in neurogenic cells. When low dose (1 μg/ml) of TiO₂ NPs entered cells, they affected mitochondrial membrane permeability and produced a small amount of superoxide anions (O₂^-⋅). The low dose of O₂^-⋅ activated the expression of mTOR protein and increased GSH production. However, TiO₂ NPs also impaired GSH-Px activity, so the antioxidant effect was weak. When cells exposed to high dose (100 μg/ml) of TiO₂ NPs, the expression of mTOR protein was inhibited by massive O₂^-⋅ from mitochondria. Moreover, high dose of TiO₂ NPs impaired the GSH-Px activity. Although GSH production was reduced, the pathway that responsible for GSH consumption was inhibited, so the intercellular GSH was still abundant.