Cerium oxide nanoparticles protect against oxidant injury and interfere with oxidative mediated kinase signaling in human-derived hepatocytes

Cerium oxide nanoparticles (CeO NPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whe...

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Detalles Bibliográficos
Autores: Carvajal, Silvia, Perramón, Meritxell|||0000-0002-1944-8337, Casals, Gregori|||0000-0002-3271-1371, Oró, Denise, Ribera Salas, Jordi|||0000-0002-0288-4220, Morales Ruiz, Manuel|||0000-0002-9074-2272, Casals, Eudald|||0000-0002-2900-7295, Casado, Pedro|||0000-0002-4207-9349, Melgar Lesmes, Pedro, Fernández-Varo, Guillermo|||0000-0002-7776-3300, Cutillas, Pedro, Puntes, Víctor|||0000-0001-8996-9499, Jiménez, Wladimiro|||0000-0002-9376-0214
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223809
Acceso en línea:https://ddd.uab.cat/record/223809
https://dx.doi.org/urn:doi:10.3390/ijms20235959
Access Level:acceso abierto
Palabra clave:Cerium oxide nanoparticles
Oxidative stress
Human hepatic cells
Phosphoproteomics
NAFLD
Descripción
Sumario:Cerium oxide nanoparticles (CeO NPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whether CeO NPs can prevent or attenuate oxidant injury in the hepatic human cell line HepG2 and to investigate the mechanisms involved in this phenomenon. The effect of CeO NPs on cell viability and ROS scavenging was determined, the differential expression of pro-inflammatory and oxidative stress-related genes was analyzed, and a proteomic analysis was performed to assess the impact of CeO NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO NPs did not modify HepG2 cell viability in basal conditions but reduced H O-and lipopolysaccharide (LPS)-induced cell death and prevented H O-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO NPs reverted the H O-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H O effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO NPs protect HepG2 cells from cell-induced oxidative damage, reducing ROS generation and inflammatory gene expression as well as regulation of kinase-driven cell survival pathways.

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