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Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium
Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957661/ https://www.ncbi.nlm.nih.gov/pubmed/33673688 http://dx.doi.org/10.3390/ijms22052401 |
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author | Bik, Ewelina Mateuszuk, Lukasz Orleanska, Jagoda Baranska, Malgorzata Chlopicki, Stefan Majzner, Katarzyna |
author_facet | Bik, Ewelina Mateuszuk, Lukasz Orleanska, Jagoda Baranska, Malgorzata Chlopicki, Stefan Majzner, Katarzyna |
author_sort | Bik, Ewelina |
collection | PubMed |
description | Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ on human microvascular endothelial cells (HMEC-1). HMEC-1 cells after CQ exposure were measured using a combined methodology based on label-free Raman and fluorescence imaging. Raman spectroscopy was applied to characterize subtle chemical changes in lipid contents and their distribution in the cells, while the fluorescence staining (LipidTox, LysoTracker and LC3) was used as a reference method. The results showed that CQ was not toxic to endothelial cells and did not result in the endothelial inflammation at concentrations of 1–30 µM. Notwithstanding, it yielded an increased intensity of LipidTox, LysoTracker, and LC3 staining, suggesting changes in the content of neutral lipids, lysosomotropism, and autophagy inhibition, respectively. The CQ-induced endothelial response was associated with lipid accumulation and was characterized by Raman spectroscopy. CQ-induced autophagosome accumulation in the endothelium is featured by a pronounced alteration in the lipid profile, but not in the endothelial inflammation. Raman-based assessment of CQ-induced biochemical changes offers a better understanding of the autophagy mechanism in the endothelial cells. |
format | Online Article Text |
id | pubmed-7957661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79576612021-03-16 Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium Bik, Ewelina Mateuszuk, Lukasz Orleanska, Jagoda Baranska, Malgorzata Chlopicki, Stefan Majzner, Katarzyna Int J Mol Sci Article Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ on human microvascular endothelial cells (HMEC-1). HMEC-1 cells after CQ exposure were measured using a combined methodology based on label-free Raman and fluorescence imaging. Raman spectroscopy was applied to characterize subtle chemical changes in lipid contents and their distribution in the cells, while the fluorescence staining (LipidTox, LysoTracker and LC3) was used as a reference method. The results showed that CQ was not toxic to endothelial cells and did not result in the endothelial inflammation at concentrations of 1–30 µM. Notwithstanding, it yielded an increased intensity of LipidTox, LysoTracker, and LC3 staining, suggesting changes in the content of neutral lipids, lysosomotropism, and autophagy inhibition, respectively. The CQ-induced endothelial response was associated with lipid accumulation and was characterized by Raman spectroscopy. CQ-induced autophagosome accumulation in the endothelium is featured by a pronounced alteration in the lipid profile, but not in the endothelial inflammation. Raman-based assessment of CQ-induced biochemical changes offers a better understanding of the autophagy mechanism in the endothelial cells. MDPI 2021-02-27 /pmc/articles/PMC7957661/ /pubmed/33673688 http://dx.doi.org/10.3390/ijms22052401 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bik, Ewelina Mateuszuk, Lukasz Orleanska, Jagoda Baranska, Malgorzata Chlopicki, Stefan Majzner, Katarzyna Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title | Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title_full | Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title_fullStr | Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title_full_unstemmed | Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title_short | Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium |
title_sort | chloroquine-induced accumulation of autophagosomes and lipids in the endothelium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957661/ https://www.ncbi.nlm.nih.gov/pubmed/33673688 http://dx.doi.org/10.3390/ijms22052401 |
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