| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 8, Iss 1, Pp 1-17 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-018-25905-8 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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