Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

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, morp...

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Autores principales:	Hasna Ahyayauch, Aritz B. García-Arribas, Jesús Sot, Emilio J. González-Ramírez, Jon V. Busto, Bingen G. Monasterio, Noemi Jiménez-Rojo, F. Xabier Contreras, Adela Rendón-Ramírez, Cesar Martin, Alicia Alonso, Félix M. Goñi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37d7248c8b5a44c8b4b2d7778320e8bc
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spelling	oai:doaj.org-article:37d7248c8b5a44c8b4b2d7778320e8bc2021-12-02T15:08:10ZPb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells10.1038/s41598-018-25905-82045-2322https://doaj.org/article/37d7248c8b5a44c8b4b2d7778320e8bc2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25905-8https://doaj.org/toc/2045-2322Abstract 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.Hasna AhyayauchAritz B. García-ArribasJesús SotEmilio J. González-RamírezJon V. BustoBingen G. MonasterioNoemi Jiménez-RojoF. Xabier ContrerasAdela Rendón-RamírezCesar MartinAlicia AlonsoFélix M. GoñiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hasna Ahyayauch Aritz B. García-Arribas Jesús Sot Emilio J. González-Ramírez Jon V. Busto Bingen G. Monasterio Noemi Jiménez-Rojo F. Xabier Contreras Adela Rendón-Ramírez Cesar Martin Alicia Alonso Félix M. Goñi Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
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.
format	article
author	Hasna Ahyayauch Aritz B. García-Arribas Jesús Sot Emilio J. González-Ramírez Jon V. Busto Bingen G. Monasterio Noemi Jiménez-Rojo F. Xabier Contreras Adela Rendón-Ramírez Cesar Martin Alicia Alonso Félix M. Goñi
author_facet	Hasna Ahyayauch Aritz B. García-Arribas Jesús Sot Emilio J. González-Ramírez Jon V. Busto Bingen G. Monasterio Noemi Jiménez-Rojo F. Xabier Contreras Adela Rendón-Ramírez Cesar Martin Alicia Alonso Félix M. Goñi
author_sort	Hasna Ahyayauch
title	Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
title_short	Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
title_full	Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
title_fullStr	Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
title_full_unstemmed	Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
title_sort	pb(ii) induces scramblase activation and ceramide-domain generation in red blood cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/37d7248c8b5a44c8b4b2d7778320e8bc
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Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

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