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Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes
Cerium oxide nanoparticles (CeO(2)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 w...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928882/ https://www.ncbi.nlm.nih.gov/pubmed/31783479 http://dx.doi.org/10.3390/ijms20235959 |
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author | Carvajal, Silvia Perramón, Meritxell Casals, Gregori Oró, Denise Ribera, Jordi Morales-Ruiz, Manuel Casals, Eudald Casado, Pedro Melgar-Lesmes, Pedro Fernández-Varo, Guillermo Cutillas, Pedro Puntes, Victor Jiménez, Wladimiro |
author_facet | Carvajal, Silvia Perramón, Meritxell Casals, Gregori Oró, Denise Ribera, Jordi Morales-Ruiz, Manuel Casals, Eudald Casado, Pedro Melgar-Lesmes, Pedro Fernández-Varo, Guillermo Cutillas, Pedro Puntes, Victor Jiménez, Wladimiro |
author_sort | Carvajal, Silvia |
collection | PubMed |
description | Cerium oxide nanoparticles (CeO(2)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(2)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(2)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(2)NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO(2)NPs did not modify HepG2 cell viability in basal conditions but reduced H(2)O(2)- and lipopolysaccharide (LPS)-induced cell death and prevented H(2)O(2)-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO(2)NPs reverted the H(2)O(2)-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H(2)O(2) effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO(2)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. |
format | Online Article Text |
id | pubmed-6928882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69288822019-12-26 Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes Carvajal, Silvia Perramón, Meritxell Casals, Gregori Oró, Denise Ribera, Jordi Morales-Ruiz, Manuel Casals, Eudald Casado, Pedro Melgar-Lesmes, Pedro Fernández-Varo, Guillermo Cutillas, Pedro Puntes, Victor Jiménez, Wladimiro Int J Mol Sci Article Cerium oxide nanoparticles (CeO(2)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(2)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(2)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(2)NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO(2)NPs did not modify HepG2 cell viability in basal conditions but reduced H(2)O(2)- and lipopolysaccharide (LPS)-induced cell death and prevented H(2)O(2)-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO(2)NPs reverted the H(2)O(2)-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H(2)O(2) effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO(2)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. MDPI 2019-11-27 /pmc/articles/PMC6928882/ /pubmed/31783479 http://dx.doi.org/10.3390/ijms20235959 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Carvajal, Silvia Perramón, Meritxell Casals, Gregori Oró, Denise Ribera, Jordi Morales-Ruiz, Manuel Casals, Eudald Casado, Pedro Melgar-Lesmes, Pedro Fernández-Varo, Guillermo Cutillas, Pedro Puntes, Victor Jiménez, Wladimiro 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 |
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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928882/ https://www.ncbi.nlm.nih.gov/pubmed/31783479 http://dx.doi.org/10.3390/ijms20235959 |
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