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Dose‑dependent autophagic effectof titanium dioxide nanoparticles in humanHaCaT cells at non‑cytotoxic levels
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. (Cristobal Lab, environmental proteomics)
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Medicine and Health Sciences.
Luxembourg Institute of Science and Technology, Luxembourg.
Stockholm University, Sweden. (Environmental Proteomics)
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2016 (English)In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 14, no 22, 1-13 p.Article in journal (Refereed) Published
Abstract [en]

Background: Interactions between nanoparticles and cells are now the focus of a fast-growing area of research.Though many nanoparticles interact with cells without any acute toxic responses, metal oxide nanoparticles includingthose composed of titanium dioxide (TiO2-NPs) may disrupt the intracellular process of macroautophagy.Autophagy plays a key role in human health and disease, particularly in cancer and neurodegenerative diseases. Weherein investigated the in vitro biological effects of TiO2-NPs (18 nm) on autophagy in human keratinocytes (HaCaT)cells at non-cytotoxic levels.Results: TiO2-NPs were characterized by transmission electron microscopy (TEM) and dynamic light scatteringtechniques. Cellular uptake, as evaluated by TEM and NanoSIMS revealed that NPs internalization led to the formationof autophagosomes. TiO2-NPs treatment did not reduce cell viability of HaCaT cells nor increased oxidative stress. Cellularautophagy was additionally evaluated by confocal microscopy using eGFP-LC3 keratinocytes, western blottingof autophagy marker LC3I/II, immunodetection of p62 and NBR1 proteins, and gene expression of LC3II, p62, NBR1,beclin1 and ATG5 by RT-qPCR. We also confirmed the formation and accumulation of autophagosomes in NPs treatedcells with LC3-II upregulation. Based on the lack of degradation of p62 and NBR1 proteins, autophagosomes accumulationat a high dose (25.0 μg/ml) is due to blockage while a low dose (0.16 μg/ml) promoted autophagy. Cellularviability was not affected in either case.Conclusions: The uptake of TiO2-NPs led to a dose-dependent increase in autophagic effect under non-cytotoxicconditions. Our results suggest dose-dependent autophagic effect over time as a cellular response to TiO2-NPs. Mostimportantly, these findings suggest that simple toxicity data are not enough to understand the full impact of TiO2-NPsand their effects on cellular pathways or function.

Place, publisher, year, edition, pages
BioMed Central, 2016. Vol. 14, no 22, 1-13 p.
Keyword [en]
Autophagy, Cell-nanoparticle interactions, Dose, Keratinocytes, Titanium dioxide nanoparticles
National Category
Cell Biology
URN: urn:nbn:se:liu:diva-126342DOI: 10.1186/s12951-016-0174-0ISI: 000372577700001PubMedID: 27001369OAI: diva2:913705
Swedish Research Council, 621-2011-5267

Funding agencies: Swedish Research Council-Natural Science; VR-NT; Carl Trygger Foundation; Oscar and Lilli Lamms Minne Foundation; Angpanneforening Research foundation; IKERBASQUE Basque Foundation for science; VINNOVA - County Councils of Ostergotland, Sweden; Linkoping 

Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2016-04-20Bibliographically approved

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