4131d73fc972d0da0f9dfd0250197289 pmc_31783479.pdf 541dac631a04ac76d54c44f55bb472138a46be91 pmc_31783479.pdf 2c106e1752243bcc48b8818b4a3f92f4e1c057f6be7557f9de61b35e16d810ff pmc_31783479.pdf Title: Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes Subject: 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. Keywords: cerium oxide nanoparticles; oxidative stress; human hepatic cells; phosphoproteomics; NAFLD Author: Silvia Carvajal, Meritxell Perramón, Gregori Casals, Denise Oró, Jordi Ribera, Manuel Morales-Ruiz, Eudald Casals, Pedro Casado, Pedro Melgar-Lesmes, Guillermo Fernández-Varo, Pedro Cutillas, Victor Puntes and Wladimiro Jiménez Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Wed Nov 27 04:29:14 2019 CET ModDate: Wed Nov 27 04:29:14 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4495896 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LWLMJK+URWPalladioL-Ital Type 1 Custom yes yes no 95 0 XPWEPJ+URWPalladioL-Bold Type 1 Custom yes yes no 96 0 ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes no 97 0 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Builtin yes yes no 564 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:16:40 CEST RepresentationInformation: pmc_31783479.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-03-09 03:41:27 CET Size: 4495896 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 2 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぃづひどふねぜ〴ぜ〰くへどつづぜ〴ぜ〰ぎちのはばちひぴどっぬづびぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰ぐひはぴづっぴぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰てひはねぜ〴ぜ〰え〲く〲〭ぜ〴ぜ〰ちのつぜ〴ぜ〰がぐこ〭どのつふっづつぜ〴ぜ〰ぃべぴはぴはへどっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぅへばひづびびどはのぜ〴ぜ〰ぐひはてどぬづぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづびぜ〴ぜ〰げづぬちぴづつぜ〴ぜ〰ぴはぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぅへばはびづつぜ〴ぜ〰ぴはぜ〴ぜ〰え〲く〲ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰げづつふっづぜ〴ぜ〰え〲く〲〭ぉのつふっづつぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰どぎくこぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰っづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ぃづひどふねぜ〴ぜ〰くへどつづぜ〴ぜ〰ぎちのはばちひぴどっぬづびぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰ぐひはぴづっぴぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰てひはねぜ〴ぜ〰え〲く〲〭ぜ〴ぜ〰ちのつぜ〴ぜ〰がぐこ〭どのつふっづつぜ〴ぜ〰ぃべぴはぴはへどっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぅへばひづびびどはのぜ〴ぜ〰ぐひはてどぬづぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづびぜ〴ぜ〰げづぬちぴづつぜ〴ぜ〰ぴはぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぅへばはびづつぜ〴ぜ〰ぴはぜ〴ぜ〰え〲く〲ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰げづつふっづぜ〴ぜ〰え〲く〲〭ぉのつふっづつぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰どぎくこぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰っづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづく〲ぎぐびぜ〴ぜ〰ぐひはぴづっぴぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰てひはねぜ〴ぜ〰え〲く〲〭ぜ〴ぜ〰ちのつぜ〴ぜ〰がぐこ〭どのつふっづつぜ〴ぜ〰ぃべぴはぴはへどっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぅへばひづびびどはのぜ〴ぜ〰ぐひはてどぬづぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづびぜ〴ぜ〰げづぬちぴづつぜ〴ぜ〰ぴはぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぅへばはびづつぜ〴ぜ〰ぴはぜ〴ぜ〰え〲く〲ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰げづつふっづぜ〴ぜ〰え〲く〲〭ぉのつふっづつぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰どぎくこぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰っづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぅへばひづびびどはのぜ〴ぜ〰ぐひはてどぬづぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづびぜ〴ぜ〰げづぬちぴづつぜ〴ぜ〰ぴはぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぅへばはびづつぜ〴ぜ〰ぴはぜ〴ぜ〰え〲く〲ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃづく〲ぎぐびぜ〴ぜ〰げづつふっづぜ〴ぜ〰え〲く〲〭ぉのつふっづつぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰どぎくこぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰っづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづく〲ぎぐびぜ〴ぜ〰げづつふっづぜ〴ぜ〰え〲く〲〭ぉのつふっづつぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰どぎくこぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲ぜ〴ぜ〰っづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぉつづのぴどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰ぎづぴぷはひにびぜ〴ぜ〰ぁててづっぴづつぜ〴ぜ〰ぢべぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰えづばぇ〲〮ぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きちぴづひどちぬぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰ぇづのづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰ぐぃげぜ〴ぜ〰ぁひひちべぜ〴ぜ〰どのぜ〴ぜ〰ぃふぬぴふひづつぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぐとはびばとはばひはぴづはねどっぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: こべのぴとづびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぃづく〲ぎぐびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰ぇづのづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰ぐぃげぜ〴ぜ〰ぁひひちべぜ〴ぜ〰どのぜ〴ぜ〰ぃふぬぴふひづつぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぐとはびばとはばひはぴづはねどっぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃづぬぬぜ〴ぜ〰ぃふぬぴふひづぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰ぇづのづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰ぐぃげぜ〴ぜ〰ぁひひちべぜ〴ぜ〰どのぜ〴ぜ〰ぃふぬぴふひづつぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぐとはびばとはばひはぴづはねどっぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰ぇづのづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰ぐぃげぜ〴ぜ〰ぁひひちべぜ〴ぜ〰どのぜ〴ぜ〰ぃふぬぴふひづつぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぐとはびばとはばひはぴづはねどっぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぐとはびばとはばひはぴづはねどっぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: 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