| Autor: |
BOUGERRA, G., TALBI, K., TRABELSI, N., HADDAD, F., CHAOUACHI, D., DARRAGI, I., BOUDRIGA, I., ABBES, S., MNIF, S. |
| Předmět: |
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| Zdroj: |
Archives de l'Institut Pasteur de Tunis; 2020, Vol. 97 Issue 1-4, p45-45, 1p |
| Abstrakt: |
Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is the most common inherited enzymopathy. It is characterized by hemolysis triggered by multiple drugs and certain foods. Defects in the G6PD enzyme enhance cellular oxidative damage, thus impairing erythrocytes and radically shortening their lifespan. Alongside hemolysis, the premature cellular breakdown could be attributed to a process of erythrocyte programmed cell death termed "eryptosis". Eryptosis is characterized by cell shrinkage and membrane blebbing with exposure of phosphatidylserine (PS) at the membrane outer leaflet. There is as yet no consistent data on PS exposure in G6PD deficiency, nor a consensus on the underlying mechanisms of premature cell death. In the present study, eryptosis was explored using annexin V-binding as an indicator of PS exposure at the erythrocyte surface in healthy donors and G6PD-deficient patients. Afterwards, the potentially-involved signaling pathways were investigated through in vitro cell stimulations by oxidation, increase of intracellular calcium concentrations, energy depletion and hyperosmolar choc. Using staining assays, reactive oxygen species as well as intracellular calcium concentrations and ceramide formation at the cell surface were assessed. Prior to and following treatments, cells were analyzed by flow cytometry. The present observations uncover a novel effect detected in G6PD-deficient erythrocytes which is cell membrane scrambling with PS translocation to the erythrocyte surface. Prior to stimulation, the percentage of PS-exposing erythrocytes was significantly higher in G6PD-deficient patients than in healthy volunteers. The increase in PS exposure was paralleled by a significant increase in reactive oxygen species production, suggesting that oxidative stress could be the main trigger of PS exposure and thus of eryptosis in G6PD-deficient erythrocytes. Furthermore, results show that in this context, neither calcium nor ceramide seem to play a major role in eryptosis pathway signaling. Taken together, these findings shed a light on the mechanisms of premature erythrocyte clearance in G6PD deficiency and suggest a potential use of the annexin V-binding assay in the biological monitoring of G6PD-deficient patients. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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