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Iron Oxide Nanoparticle-Induced Autophagic Flux Is Regulated by Interplay between p53-mTOR Axis and Bcl-2 Signaling in Hepatic Cells

1
Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
2
Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic
3
Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(4), 1015; https://doi.org/10.3390/cells9041015
Received: 13 March 2020 / Revised: 10 April 2020 / Accepted: 15 April 2020 / Published: 18 April 2020
Iron oxide-based nanoparticles have been repeatedly shown to affect lysosomal-mediated signaling. Recently, nanoparticles have demonstrated an ability to modulate autophagic flux via lysosome-dependent signaling. However, the precise underlying mechanisms of such modulation as well as the impact of cellular genetic background remain enigmatic. In this study, we investigated how lysosomal-mediated signaling is affected by iron oxide nanoparticle uptake in three distinct hepatic cell lines. We found that nanoparticle-induced lysosomal dysfunction alters sub-cellular localization of pmTOR and p53 proteins. Our data indicate that alterations in the sub-cellular localization of p53 protein induced by nanoparticle greatly affect the autophagic flux. We found that cells with high levels of Bcl-2 are insensitive to autophagy initiated by nanoparticles. Altogether, our data identify lysosomes as a central hub that control nanoparticle-mediated responses in hepatic cells. Our results provide an important fundamental background for the future development of targeted nanoparticle-based therapies.
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Keywords: nano-bio interactions; iron oxide nanoparticles; autophagy; lysosomes; magnetic resonance imaging; p53 nano-bio interactions; iron oxide nanoparticles; autophagy; lysosomes; magnetic resonance imaging; p53
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MDPI and ACS Style

Uzhytchak, M.; Smolková, B.; Lunova, M.; Jirsa, M.; Frtús, A.; Kubinová, Š.; Dejneka, A.; Lunov, O. Iron Oxide Nanoparticle-Induced Autophagic Flux Is Regulated by Interplay between p53-mTOR Axis and Bcl-2 Signaling in Hepatic Cells. Cells 2020, 9, 1015. https://doi.org/10.3390/cells9041015

AMA Style

Uzhytchak M, Smolková B, Lunova M, Jirsa M, Frtús A, Kubinová Š, Dejneka A, Lunov O. Iron Oxide Nanoparticle-Induced Autophagic Flux Is Regulated by Interplay between p53-mTOR Axis and Bcl-2 Signaling in Hepatic Cells. Cells. 2020; 9(4):1015. https://doi.org/10.3390/cells9041015

Chicago/Turabian Style

Uzhytchak, Mariia, Barbora Smolková, Mariia Lunova, Milan Jirsa, Adam Frtús, Šárka Kubinová, Alexandr Dejneka, and Oleg Lunov. 2020. "Iron Oxide Nanoparticle-Induced Autophagic Flux Is Regulated by Interplay between p53-mTOR Axis and Bcl-2 Signaling in Hepatic Cells" Cells 9, no. 4: 1015. https://doi.org/10.3390/cells9041015

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