Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes

Cerium oxide nanoparticles (CeO2NPs) 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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Autores: Carvajal Romero, Silvia, Perramón Corominas, Meritxell, Casals Mercadal, Gregori, Oró Bozzini, Denise, Ribera Sabaté, Jordi, Morales Ruiz, Manuel, Casals, Eudald, Casado, Pedro, Melgar-Lesmes, Pedro, Fernández Varo, Guillermo, Cutillas, Pedro R., Puntes, Víctor, Jiménez Povedano, Wladimiro
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176106
Acesso em linha:https://hdl.handle.net/2445/176106
Access Level:Acceso aberto
Palavra-chave:Ceri (Element químic)
Estrès oxidatiu
Cèl·lules hepàtiques
Cerium
Oxidative stress
Liver cells
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spelling Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived HepatocytesCarvajal Romero, SilviaPerramón Corominas, Meritxell Casals Mercadal, GregoriOró Bozzini, DeniseRibera Sabaté, JordiMorales Ruiz, ManuelCasals, EudaldCasado, PedroMelgar-Lesmes, PedroFernández Varo, GuillermoCutillas, Pedro R.Puntes, VíctorJiménez Povedano, WladimiroCeri (Element químic)Estrès oxidatiuCèl·lules hepàtiquesCeriumOxidative stressLiver cellsCerium oxide nanoparticles (CeO2NPs) 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 CeO2NPs 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 CeO2NPs 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 CeO2NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO2NPs did not modify HepG2 cell viability in basal conditions but reduced H2O2- and lipopolysaccharide (LPS)-induced cell death and prevented H2O2-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO2NPs reverted the H2O2-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H2O2 effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO2NPs 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.MDPI2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/176106Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms20235959International Journal of Molecular Sciences, 2019, vol. 20, num. 23, p. 5959https://doi.org/10.3390/ijms20235959cc-by (c) Carvajal Romero, Silvia et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1761062026-05-27T06:46:51Z
dc.title.none.fl_str_mv Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
title Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
spellingShingle Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
Carvajal Romero, Silvia
Ceri (Element químic)
Estrès oxidatiu
Cèl·lules hepàtiques
Cerium
Oxidative stress
Liver cells
title_short Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
title_full Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
title_fullStr Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
title_full_unstemmed Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
title_sort Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
dc.creator.none.fl_str_mv Carvajal Romero, Silvia
Perramón Corominas, Meritxell
Casals Mercadal, Gregori
Oró Bozzini, Denise
Ribera Sabaté, Jordi
Morales Ruiz, Manuel
Casals, Eudald
Casado, Pedro
Melgar-Lesmes, Pedro
Fernández Varo, Guillermo
Cutillas, Pedro R.
Puntes, Víctor
Jiménez Povedano, Wladimiro
author Carvajal Romero, Silvia
author_facet Carvajal Romero, Silvia
Perramón Corominas, Meritxell
Casals Mercadal, Gregori
Oró Bozzini, Denise
Ribera Sabaté, Jordi
Morales Ruiz, Manuel
Casals, Eudald
Casado, Pedro
Melgar-Lesmes, Pedro
Fernández Varo, Guillermo
Cutillas, Pedro R.
Puntes, Víctor
Jiménez Povedano, Wladimiro
author_role author
author2 Perramón Corominas, Meritxell
Casals Mercadal, Gregori
Oró Bozzini, Denise
Ribera Sabaté, Jordi
Morales Ruiz, Manuel
Casals, Eudald
Casado, Pedro
Melgar-Lesmes, Pedro
Fernández Varo, Guillermo
Cutillas, Pedro R.
Puntes, Víctor
Jiménez Povedano, Wladimiro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ceri (Element químic)
Estrès oxidatiu
Cèl·lules hepàtiques
Cerium
Oxidative stress
Liver cells
topic Ceri (Element químic)
Estrès oxidatiu
Cèl·lules hepàtiques
Cerium
Oxidative stress
Liver cells
description Cerium oxide nanoparticles (CeO2NPs) 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 CeO2NPs 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 CeO2NPs 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 CeO2NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO2NPs did not modify HepG2 cell viability in basal conditions but reduced H2O2- and lipopolysaccharide (LPS)-induced cell death and prevented H2O2-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO2NPs reverted the H2O2-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H2O2 effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO2NPs 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/176106
url https://hdl.handle.net/2445/176106
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms20235959
International Journal of Molecular Sciences, 2019, vol. 20, num. 23, p. 5959
https://doi.org/10.3390/ijms20235959
dc.rights.none.fl_str_mv cc-by (c) Carvajal Romero, Silvia et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Carvajal Romero, Silvia et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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