Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis
Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated...
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pubmed-44191522015-05-11 Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis Strobel, Claudia Oehring, Hartmut Herrmann, Rudolf Förster, Martin Reller, Armin Hilger, Ingrid Research Paper Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells. Springer Netherlands 2015-05-05 2015 /pmc/articles/PMC4419152/ /pubmed/25972759 http://dx.doi.org/10.1007/s11051-015-3007-4 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
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Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Strobel, Claudia Oehring, Hartmut Herrmann, Rudolf Förster, Martin Reller, Armin Hilger, Ingrid |
spellingShingle |
Strobel, Claudia Oehring, Hartmut Herrmann, Rudolf Förster, Martin Reller, Armin Hilger, Ingrid Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
author_facet |
Strobel, Claudia Oehring, Hartmut Herrmann, Rudolf Förster, Martin Reller, Armin Hilger, Ingrid |
author_sort |
Strobel, Claudia |
title |
Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
title_short |
Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
title_full |
Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
title_fullStr |
Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
title_full_unstemmed |
Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
title_sort |
fate of cerium dioxide nanoparticles in endothelial cells: exocytosis |
description |
Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells. |
publisher |
Springer Netherlands |
publishDate |
2015 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419152/ |
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1613218923567644672 |