Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases

Recent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biology, and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we...

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Autores: Ibanez, F, Montesinos, J, Area-Gomez, E, Guerri, C, Pascual, M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p3781
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3781
Access Level:acceso abierto
Palabra clave:extracellular vesicles
lipid metabolism
mitochondria-associated ER membranes
alcohol
neuroinflammation
microglia
sphingomyelinases
phospholipids
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spelling Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and SphingomyelinasesIbanez, FMontesinos, JArea-Gomez, EGuerri, CPascual, Mextracellular vesicleslipid metabolismmitochondria-associated ER membranesalcoholneuroinflammationmicrogliasphingomyelinasesphospholipidsRecent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biology, and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we evaluated if MAMs and sphingomyelinases (SMases) could participate in ethanol-induced EV release. EVs were isolated from the extracellular medium of BV2 microglia treated or not with ethanol (50 and 100 mM). Radioactive metabolic tracers combined with thin layer chromatography were used as quantitative methods to assay phospholipid transfer, SMase activity and cholesterol uptake/esterification. Inhibitors of SMase (desipramine and GW4869) and MAM (cyclosporin A) activities were also utilized. Our data show that ethanol increases the secretion and inflammatory molecule concentration of EVs. Ethanol also upregulates MAM activity and alters lipid metabolism by increasing cholesterol uptake, cholesterol esterification and SMase activity in microglia. Notably, the inhibition of either SMase or MAM activity prevented the ethanol-induced increase in EV secretion. Collectively, these results strongly support a lipid-driven mechanism, specifically via SMases and MAM, to explain the effect of ethanol on EV secretion in glial cells.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3781INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 14220067reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p37812026-06-17T11:19:47Z
dc.title.none.fl_str_mv Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
title Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
spellingShingle Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
Ibanez, F
extracellular vesicles
lipid metabolism
mitochondria-associated ER membranes
alcohol
neuroinflammation
microglia
sphingomyelinases
phospholipids
title_short Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
title_full Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
title_fullStr Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
title_full_unstemmed Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
title_sort Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases
dc.creator.none.fl_str_mv Ibanez, F
Montesinos, J
Area-Gomez, E
Guerri, C
Pascual, M
author Ibanez, F
author_facet Ibanez, F
Montesinos, J
Area-Gomez, E
Guerri, C
Pascual, M
author_role author
author2 Montesinos, J
Area-Gomez, E
Guerri, C
Pascual, M
author2_role author
author
author
author
dc.subject.none.fl_str_mv extracellular vesicles
lipid metabolism
mitochondria-associated ER membranes
alcohol
neuroinflammation
microglia
sphingomyelinases
phospholipids
topic extracellular vesicles
lipid metabolism
mitochondria-associated ER membranes
alcohol
neuroinflammation
microglia
sphingomyelinases
phospholipids
description Recent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biology, and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we evaluated if MAMs and sphingomyelinases (SMases) could participate in ethanol-induced EV release. EVs were isolated from the extracellular medium of BV2 microglia treated or not with ethanol (50 and 100 mM). Radioactive metabolic tracers combined with thin layer chromatography were used as quantitative methods to assay phospholipid transfer, SMase activity and cholesterol uptake/esterification. Inhibitors of SMase (desipramine and GW4869) and MAM (cyclosporin A) activities were also utilized. Our data show that ethanol increases the secretion and inflammatory molecule concentration of EVs. Ethanol also upregulates MAM activity and alters lipid metabolism by increasing cholesterol uptake, cholesterol esterification and SMase activity in microglia. Notably, the inhibition of either SMase or MAM activity prevented the ethanol-induced increase in EV secretion. Collectively, these results strongly support a lipid-driven mechanism, specifically via SMases and MAM, to explain the effect of ethanol on EV secretion in glial cells.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3781
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3781
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 14220067
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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