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Proteomic and lipidomic analysis of primary mouse hepatocytes exposed to metal and metal oxide nanoparticles
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. (Environmental proteomics, Cell Biology section)ORCID iD: 0000-0002-3894-2218
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. (Environmental Proteomics, Cell Biology section)
Stockholm University. (Environmental Proteomics)
Stockholm University. (Environmental Proteomics)
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2015 (English)In: Journal of Integrated OMICS, ISSN 2182-0287, Vol. 5, no 1, 44-57 p.Article in journal (Refereed) Published
Abstract [en]

The global analysis of the cellular lipid and protein content upon exposure to metal and metal oxide nanoparticles (NPs) can provide an overviewof the possible impact of exposure. Proteomic analysis has been applied to understand the nanoimpact however the relevance of the alterationon the lipidic proOle has been underestimated. In our study, primary mouse hepatocytes were treated with ultra-small (US) TiO2-USNPsas well as ZnO-NPs, CuO-NPs and Ag-NPs. e protein extracts were analysed by 2D-DIGE and quantiOed by imaging soPware and the selecteddi9erentially expressed proteins were identiOed by nLC-ESI-MS/MS. In parallel, lipidomic analysis of the samples was performed usingthin layer chromatography (TLC) and analyzed by imaging soPware. Our Ondings show an overall ranking of the nanoimpact at the cellularand molecular level: TiO2-USNPs<ZnO-NPs<Ag-NPs<CuO-NPs. CuO-NPs and Ag-NPs were cytotoxic while ZnO-NPs and CuO-NPs hadoxidative capacity. TiO2-USNPs did not have oxidative capacity and were not cytotoxic. e most common cellular impact of the exposurewas the down-regulation of proteins. e proteins identiOed were involved in urea cycle, lipid metabolism, electron transport chain, metabolismsignaling, cellular structure and we could also identify nuclear proteins. CuO-NPs exposure decreased phosphatidylethanolamine andphosphatidylinositol and caused down-regulation of electron transferring protein subunit beta. Ag-NPs exposure caused increased of totallipids and triacylglycerol and decrease of sphingomyelin. TiO2-USNPs also caused decrease of sphingomyelin as well as up-regulation of ATPsynthase and electron transferring protein alfa. ZnO-NPs a9ected the proteome in a concentration-independent manner with down-regulationof RNA helicase. ZnO-NPs exposure did not a9ect the cellular lipids. To our knowledge this work represents the Orst integrated proteomic andlipidomic approach to study the e9ect of NPs exposure to primary mouse hepatocytes in vitro.

Place, publisher, year, edition, pages
2015. Vol. 5, no 1, 44-57 p.
Keyword [en]
nanoparticles; hepatocytes; proteomics; lipidomics; mass spectrometry; toxicity
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:liu:diva-115894DOI: 10.5584/jiomics.v5i1.184OAI: diva2:797186
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2015-10-28Bibliographically approved

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Cristobal, SusanaTedesco, Sara
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