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 (H<sub>2</sub>O<sub>2</sub>), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H<sub>2</sub>O<sub>2</sub>, and t...

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Main Authors: Giorgia Pellavio, Patrizia Sommi, Umberto Anselmi-Tamburini, Maria Paola DeMichelis, Stefania Coniglio, Umberto Laforenza
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/18/10837
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author Giorgia Pellavio
Patrizia Sommi
Umberto Anselmi-Tamburini
Maria Paola DeMichelis
Stefania Coniglio
Umberto Laforenza
author_facet Giorgia Pellavio
Patrizia Sommi
Umberto Anselmi-Tamburini
Maria Paola DeMichelis
Stefania Coniglio
Umberto Laforenza
author_sort Giorgia Pellavio
collection DOAJ
description Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H<sub>2</sub>O<sub>2</sub>, 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 H<sub>2</sub>O<sub>2</sub>. 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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.
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spelling doaj.art-a34ae24d57364ff58269a1c76d160c302023-11-23T16:48:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181083710.3390/ijms231810837Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide PermeabilityGiorgia Pellavio0Patrizia Sommi1Umberto Anselmi-Tamburini2Maria Paola DeMichelis3Stefania Coniglio4Umberto Laforenza5Department of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, ItalyDepartment of Chemistry, University of Pavia, 27100 Pavia, ItalyDepartment of Chemistry, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, ItalySome aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H<sub>2</sub>O<sub>2</sub>, 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 H<sub>2</sub>O<sub>2</sub>. 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/1422-0067/23/18/10837CeO<sub>2</sub>HeLananoparticleswater channelsperoxiporinHyPer7 probe
spellingShingle Giorgia Pellavio
Patrizia Sommi
Umberto Anselmi-Tamburini
Maria Paola DeMichelis
Stefania Coniglio
Umberto Laforenza
Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
International Journal of Molecular Sciences
CeO<sub>2</sub>
HeLa
nanoparticles
water channels
peroxiporin
HyPer7 probe
title Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
title_full Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
title_fullStr Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
title_full_unstemmed Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
title_short Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability
title_sort cerium oxide nanoparticles regulate oxidative stress in hela cells by increasing the aquaporin mediated hydrogen peroxide permeability
topic CeO<sub>2</sub>
HeLa
nanoparticles
water channels
peroxiporin
HyPer7 probe
url https://www.mdpi.com/1422-0067/23/18/10837
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