Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H₂O₂), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H₂O₂, and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose. This study aimed to analyze the effect of cerium oxide nanoparticles (CNPs) presenting antioxidant activity on AQP functioning. HeLa cells express AQP3, 6, 8, and 11, able to facilitate H₂O₂. AQP3, 6, and 8 are expressed in the plasma membrane and intracellularly, while AQP11 resides only in intracellular structures. CNPs but not cerium ions treatment significantly increased the water and H₂O₂ permeability by interacting with AQP3, 6, and especially with AQP8. CNPs increased considerably the AQP-mediated water diffusion in cells with oxidative stress. Functional experiments with silenced HeLa cells revealed that CNPs increased the H₂O₂ diffusion mainly by modulating the AQP8 permeability but also the AQP3 and AQP6, even if to a lesser extent. Current findings suggest that CNPs represent a promising pharmaceutical agent that might potentially be used in numerous pathologies involving oxidative stress as tumors and neurodegenerative diseases.