Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells
| Autor: | Emilio J. González-Ramírez, César Martín, Bingen G. Monasterio, Aritz B. García-Arribas, Noemi Jiménez-Rojo, Jesús Sot, Jon V. Busto, F.-Xabier Contreras, Hasna Ahyayauch, Adela Rendón-Ramírez, Félix M. Goñi, Alicia Alonso |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
phospholipid scramblase Ceramide transbilayer movement Phospholipid scramblase Erythrocytes Science chemistry.chemical_element CHO Cells Calcium Ceramides Hemolysis Article 03 medical and health sciences Immunolabeling chemistry.chemical_compound Cricetulus Animals Humans Phospholipid Transfer Proteins sphingomyelinase activity Multidisciplinary Chemistry phosphatidylserine exposure biochemical-evidence apoptotic cells Cell sorting Sphingolipid flop lipid motion Potassium channel Cell biology Enzyme Activation 030104 developmental biology Lead Medicine Sphingomyelin plasma-membranes |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-17 (2018) Addi. Archivo Digital para la Docencia y la Investigación instname Scientific Reports |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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