Zinc-induced suicidal erythrocyte death

Abstract

Background: Zn2+ stimulates secretory sphingomyelinase, which in turn produces ceramide, an important trigger of suicidal erythrocyte death or eryptosis. Eryptosis is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. As macrophages are equipped with PS receptors, they bind, engulf, and degrade PS-exposing cells. Objective: We examined whether Zn2+ stimulates ceramide formation and PS exposure of erythrocytes and thus may be able to trigger suicidal erythrocyte death. Design: In erythrocytes from healthy volunteers, PS exposure (Annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anticeramide antibody) were determined by fluorescence-assisted cell sorting. Results: Exposure to Zn 2+ (≥25 μmol/L Zn2+) significantly increased annexin binding. The effect was paralleled by increase of cytosolic Ca2+ activity (≥25 μmol/L Zn2+) and by ceramide formation (≥10 μmol/L Zn2+). Glucose depletion (24 h) similarly increased PS exposure, an effect significantly enhanced in the presence of Zn2+ (≥10 μmol/L Zn2+). Conclusion: Zn2+ triggers suicidal erythrocyte death, an effect partially due to ceramide formation and an increase of cytosolic Ca2+ activity. © 2008 American Society for Nutrition.