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

被引：36

作者：

Carvajal, Silvia ^{[1
]}

Perramon, Meritxell ^{[1
]}

Casals, Gregori ^{[1
]}

Oro, Denise ^{[1
]}

Ribera, Jordi ^{[1
]}

Morales-Ruiz, Manuel ^{[1
,2
]}

Casals, Eudald ^{[3
]}

Casado, Pedro ^{[4
]}

Melgar-Lesmes, Pedro ^{[1
,2
]}

Fernandez-Varo, Guillermo ^{[1
,2
]}

Cutillas, Pedro ^{[4
]}

Puntes, Victor ^{[5
,6
,7
]}

Jimenez, Wladimiro ^{[1
,2
]}

机构：

[1] Hosp Clin Univ, IDIBAPS, CIBERehd, Biochem & Mol Genet Serv, Barcelona 08036, Spain

[2] Univ Barcelona, Dept Biomed, E-08036 Barcelona, Spain

[3] Wuyi Univ, Sch Biotechnol & Hlth Sci, Jiangmen 529020, Peoples R China

[4] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, Cell Signalling & Prote Grp, London EC1M 6BQ, England

[5] ICREA, Barcelona 08010, Spain

[6] VHIR, Barcelona 08035, Spain

[7] ICN2, Bellaterra 08193, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 23期

关键词：

cerium oxide nanoparticles; oxidative stress; human hepatic cells; phosphoproteomics; NAFLD; STRESS; GENE; RATS; IDENTIFICATION; ACTIVATION; DISCOVERY; APOPTOSIS; TOXICITY; FIBROSIS; BREAST;

D O I：

10.3390/ijms20235959

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 H2O2- and lipopolysaccharide (LPS)-induced cell death and prevented H2O2-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO(2)NPs 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, 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.

引用

页数：22

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