(1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol

The discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolip...

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Authors: González-Ramírez, Emilio J., García-Arribas, Aritz B., Artetxe, Ibai, Shaw, W. A., Goñi, Félix M., Alonso, Alicia, Jiménez-Rojo, Noemí
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372769
Online Access:http://hdl.handle.net/10261/372769
https://api.elsevier.com/content/abstract/scopus_id/85201013945
Access Level:Open access
Keyword:Deoxyceramides
Sphingolipids
Gel phases
Differential scanning calorimetry
Atomic force microscopy
Confocal fluorescence microscopy
Lipid-lipid interactions
Force spectroscopy
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spelling (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterolGonzález-Ramírez, Emilio J.García-Arribas, Aritz B.Artetxe, IbaiShaw, W. A.Goñi, Félix M.Alonso, AliciaJiménez-Rojo, NoemíDeoxyceramidesSphingolipidsGel phasesDifferential scanning calorimetryAtomic force microscopyConfocal fluorescence microscopyLipid-lipid interactionsForce spectroscopyThe discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolipids and they were more toxic when accumulated in cells, inducing neurodegeneration and other dysfunctions. (1-Deoxy)ceramides, (1-deoxy)dihydroceramides, and (1- deoxymethyl)dihydroceramides, the latter two containing a saturated sphingoid chain, have been studied in this work using differential scanning calorimetry, confocal fluorescence and atomic force microscopy, to evaluate their behavior in bilayers composed of mixtures of three or four lipids. When compared to canonical ceramides (Cer), a C16:0 (1-deoxy)Cer shows a lower miscibility in mixtures of the kind C16:0 sphingomyelin/cholesterol/XCer, where XCer is any (1-deoxy)ceramide, giving rise to the coexistence of a liquid-ordered phase and a gel phase. The latter resembles, in terms of thermotropic behavior and nanomechanical resistance, the gel phase of the C16:0 sphingomyelin/cholesterol/C16:0 Cer mixture [Busto et al., Biophys. J. 2014, 106, 621-630]. Differences are seen between the various C16:0 XCer under study in terms of nanomechanical resistance, bilayer thickness and bilayer topography. When examined in a more fluid environment (bilayers based on C24:1 SM), segregated gel phases are still present. Probably related to such lateral separation, XCer preserve the capacity for membrane permeation, but their effects are significantly lower than those of canonical ceramides. Moreover, C24:1 XCer show significantly lower membrane permeation capacity than their C16:0 counterparts. The above data may be relevant in the pathogenesis of certain sphingolipid-related diseases, including certain neuropathies, diabetes, and glycogen storage diseases.This work was funded in part by the Spanish Ministry of Science, Innovation, and Universities (MCIU), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER) (grant No. PID2021–124461NB-I00), the Basque Government (grant No. IT1625–22), Fundación Ramón Areces (CIVP20A6619), Fundación Biofísica Bizkaia, and the Basque Excellence Research Centre (BERC) program of the Basque Government. AGA and NJR were supported by the Basque Government and by the University of the Basque Country (UPV/EHU). AGA also received a postdoctoral grant from UPV/EHU. IA was a predoctoral student supported by UPV/EHU.Peer reviewedElsevierMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionEusko JaurlaritzaFundación Ramón ArecesFundación Biofísica BizkaiaBasque Excellence Research CentreUniversidad del País VascoConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/372769https://api.elsevier.com/content/abstract/scopus_id/85201013945reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124461NB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.colsurfb.2024.114155https://doi.org/10.1016/j.colsurfb.2024.114155Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3727692026-05-22T06:33:51Z
dc.title.none.fl_str_mv (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
title (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
spellingShingle (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
González-Ramírez, Emilio J.
Deoxyceramides
Sphingolipids
Gel phases
Differential scanning calorimetry
Atomic force microscopy
Confocal fluorescence microscopy
Lipid-lipid interactions
Force spectroscopy
title_short (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
title_full (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
title_fullStr (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
title_full_unstemmed (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
title_sort (1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol
dc.creator.none.fl_str_mv González-Ramírez, Emilio J.
García-Arribas, Aritz B.
Artetxe, Ibai
Shaw, W. A.
Goñi, Félix M.
Alonso, Alicia
Jiménez-Rojo, Noemí
author González-Ramírez, Emilio J.
author_facet González-Ramírez, Emilio J.
García-Arribas, Aritz B.
Artetxe, Ibai
Shaw, W. A.
Goñi, Félix M.
Alonso, Alicia
Jiménez-Rojo, Noemí
author_role author
author2 García-Arribas, Aritz B.
Artetxe, Ibai
Shaw, W. A.
Goñi, Félix M.
Alonso, Alicia
Jiménez-Rojo, Noemí
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Eusko Jaurlaritza
Fundación Ramón Areces
Fundación Biofísica Bizkaia
Basque Excellence Research Centre
Universidad del País Vasco
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Deoxyceramides
Sphingolipids
Gel phases
Differential scanning calorimetry
Atomic force microscopy
Confocal fluorescence microscopy
Lipid-lipid interactions
Force spectroscopy
topic Deoxyceramides
Sphingolipids
Gel phases
Differential scanning calorimetry
Atomic force microscopy
Confocal fluorescence microscopy
Lipid-lipid interactions
Force spectroscopy
description The discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolipids and they were more toxic when accumulated in cells, inducing neurodegeneration and other dysfunctions. (1-Deoxy)ceramides, (1-deoxy)dihydroceramides, and (1- deoxymethyl)dihydroceramides, the latter two containing a saturated sphingoid chain, have been studied in this work using differential scanning calorimetry, confocal fluorescence and atomic force microscopy, to evaluate their behavior in bilayers composed of mixtures of three or four lipids. When compared to canonical ceramides (Cer), a C16:0 (1-deoxy)Cer shows a lower miscibility in mixtures of the kind C16:0 sphingomyelin/cholesterol/XCer, where XCer is any (1-deoxy)ceramide, giving rise to the coexistence of a liquid-ordered phase and a gel phase. The latter resembles, in terms of thermotropic behavior and nanomechanical resistance, the gel phase of the C16:0 sphingomyelin/cholesterol/C16:0 Cer mixture [Busto et al., Biophys. J. 2014, 106, 621-630]. Differences are seen between the various C16:0 XCer under study in terms of nanomechanical resistance, bilayer thickness and bilayer topography. When examined in a more fluid environment (bilayers based on C24:1 SM), segregated gel phases are still present. Probably related to such lateral separation, XCer preserve the capacity for membrane permeation, but their effects are significantly lower than those of canonical ceramides. Moreover, C24:1 XCer show significantly lower membrane permeation capacity than their C16:0 counterparts. The above data may be relevant in the pathogenesis of certain sphingolipid-related diseases, including certain neuropathies, diabetes, and glycogen storage diseases.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/372769
https://api.elsevier.com/content/abstract/scopus_id/85201013945
url http://hdl.handle.net/10261/372769
https://api.elsevier.com/content/abstract/scopus_id/85201013945
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124461NB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.colsurfb.2024.114155
https://doi.org/10.1016/j.colsurfb.2024.114155
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.name.fl_str_mv
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