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

Scientific Reports
Hasna AhyayauchFélix M Goñi

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...Continue Reading

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Citations

Apr 16, 2020·International Journal of Molecular Sciences·Bingen G MonasterioAlicia Alonso
Nov 27, 2019·Chemical Research in Toxicology·Santosh Kumar Palanirajan, Sathyanarayana N Gummadi
Jun 3, 2020·Biochimica Et Biophysica Acta. Biomembranes·K A MelzakK Bieback
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Apr 17, 2021·Environmental Science and Pollution Research International·Maryam RezaeiGeir Bjørklund
May 5, 2021·Ecotoxicology and Environmental Safety·Na QiaoZhaoxin Tang
May 20, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bingen G MonasterioAlicia Alonso
Jul 13, 2021·Analytica Chimica Acta·Xiaqing ZhuZefang Wang
Aug 11, 2021·Journal of Agricultural and Food Chemistry·Peirong CaiJianchun Bian

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Methods Mentioned

BETA
transfection
confocal microscopy
fluorescence-activated cell sorting
FACS
Atomic Force Microscopy
AFM
mechanical stress
differential scanning calorimetry
flow cytometry
fluorescence microscopy

Software Mentioned

JPK Data Processing

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