Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
dc.contributor.author | Ahyayauch, Hasna | |
dc.contributor.author | García Arribas, Aritz | |
dc.contributor.author | Sot, Jesús | |
dc.contributor.author | González Ramírez, Emilio José | |
dc.contributor.author | Busto Gamero, Jon V. | |
dc.contributor.author | Gutiérrez Monasterio, Bingen | |
dc.contributor.author | Jiménez Rojo, Noemi | |
dc.contributor.author | Contreras Gómez, Xabier | |
dc.contributor.author | Rendón Ramírez, Adela | |
dc.contributor.author | Martín Plágaro, César Augusto | |
dc.contributor.author | Alonso Izquierdo, Alicia | |
dc.contributor.author | Goñi Urcelay, Félix María | |
dc.date.accessioned | 2018-11-15T11:02:29Z | |
dc.date.available | 2018-11-15T11:02:29Z | |
dc.date.issued | 2018-05-10 | |
dc.identifier.citation | Scientific Reports 8 : (2018) // Article ID 7456 | es_ES |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/29664 | |
dc.description.abstract | The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling. | es_ES |
dc.description.sponsorship | AGA was a predoctoral student supported by the Basque Government and later by the University of the Basque Country (UPV/EHU). This work was also supported in part by grants from the Spanish Government (FEDER/MINECO BFU 2015-66306-P to F.M.G. and A.A.) and the Basque Government (IT849-13 to F.M.G. and IT838-13 to A.A.), and by the Swiss National Science Foundation. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU 2015-66306-P | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | flop lipid motion | es_ES |
dc.subject | phospholipid scramblase | es_ES |
dc.subject | phosphatidylserine exposure | es_ES |
dc.subject | transbilayer movement | es_ES |
dc.subject | apoptotic cells | es_ES |
dc.subject | sphingomyelinase activity | es_ES |
dc.subject | biochemical-evidence | es_ES |
dc.subject | plasma-membranes | es_ES |
dc.title | Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.relation.publisherversion | https://www.nature.com/articles/s41598-018-25905-8.pdf | es_ES |
dc.identifier.doi | 10.1038/s41598-018-25905-8 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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