Amyloid induced suicidal erythrocyte death

Amyloid peptides are known to induce apoptosis in a wide variety of cells. Erythrocytes may similarly undergo suicidal death or eryptosis, which is characterized by scrambling of the cell membrane with subsequent exposure of phosphatidylserine ( PS) at the cell surface. Eryptosis is triggered by increase of cytosolic Ca2+ activity and by activation of acid sphingomyelinase with subsequent formation of ceramide. Triggers of eryptosis include energy depletion and isosmotic cell shrinkage (replacement of extracellular Cl- by impermeable gluconate for 24 h). The present study explored whether amyloid peptide A beta(1-42) could trigger eryptosis and to possibly identify underlying mechanisms. Erythrocytes from healthy volunteers were exposed to amyloid and PS-exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence) and ceramide formation (anti-ceramide antibody) were determined by FACS analysis. Exposure of erythrocytes to the amyloid peptide A beta(1-42) (>= 0.5 mu M) for 24 h significantly triggered annexin V binding, an effect mimicked to a lesser extent by the amyloid peptide A beta(1-40) (1 mu M). A beta(1-42) (>= 1.0 mu M) further significantly decreased forward scatter of erythrocytes. The effect of A beta(1-42) (>= 0.5 mu M) on erythrocyte annexin V binding was paralleled by formation of ceramide but not by significant increase of cytosolic Ca2+ activity. The presence of A beta(1-42) further significantly enhanced the eryptosis following Cl- depletion but not of glucose depletion for 24 hours. The present observations disclose a novel action of A beta(1-42), which may well contribute to the pathophysiological effects of amyloid peptides, such as vascular complications in Alzheimer's disease. Copyright (c) 2007 S. Karger AG, Basel.