Monensin Induced Suicidal Erythrocyte Death

[摘要] Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca²⁺ concentration. Eryptosis is further stimulated by the K⁺ ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na⁺/K⁺ ATPase thus increasing cytosolic Na⁺ concentration. The present study explored whether the Na⁺ ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca²⁺ concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 µg/ml) significantly increased forward scatter, cytosolic Ca²⁺ concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca²⁺ concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca²⁺ concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.

[学科分类] 分子生物学，细胞生物学和基因

[关键词] Phosphatidylserine;Monensin;Scrambling;Calcium;Cell volume;Eryptosis;Glucose depletion;Apoptosis