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...

Full description

Bibliographic Details
Main Authors: Strobel, Claudia, Oehring, Hartmut, Herrmann, Rudolf, Förster, Martin, Reller, Armin, Hilger, Ingrid
Format: Online
Language:English
Published: Springer Netherlands 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419152/
id pubmed-4419152
recordtype oai_dc
spelling 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.
repository_type 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/
_version_ 1613218923567644672