Amyloid Induced Suicidal Erythrocyte Death

Abstract

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 Aβ _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 Aβ _1-42 (? 0.5 µM) for 24 h significantly triggered annexin V binding, an effect mimicked to a lesser extent by the amyloid peptide Aβ _1-40 (1 µM). Aβ _1-42 (? 1.0 µM) further significantly decreased forward scatter of erythrocytes. The effect of Aβ _1-42 (? 0.5 µM) on erythrocyte annexin V binding was paralleled by formation of ceramide but not by significant increase of cytosolic Ca²⁺ activity. The presence of Aβ _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 Aβ _1-42, which may well contribute to the pathophysiological effects of amyloid peptides, such as vascular complications in Alzheimer''s disease.

Hemin-induced suicidal erythrocyte death

“…Some of these diseases may cause eryptosis by stimulating the formation of hemin. Furthermore, several eryptosis-triggering xenobiotics and endogeneous substances have been identified, such as cordycepin [50], methylglyoxal [54], amyloid peptides [53], lipopetides [71] retinoic acid [55], paclitaxel [44], amantadine [23], chlorpromazine [1], ciglitazone [58], cyclosporine [56], Bay-5884 [65], curcumin [4], valinomycin [64], listeriolysin [25], aluminum [57], copper [46], bismuth [13], tin [52], cadmium [68], selenium [67], vanadate [27], gold [69], and arsenic [51]. At least in theory, some of those substances may be effective through stimulation of hemin formation.…”

Stimulation of Eryptosis by Cadmium Ions

“…Eryptosis has been observed in a wide variety of further anemic conditions, including sickle-cell anemia [59,60], beta-thalassemia [55], glucose-6-phosphate dehydrogenase (G6PD)-deficiency [55], phosphate depletion [59], iron deficiency [61], Hemolytic Uremic Syndrome [62], sepsis [63], malaria [64] and Wilson disease [35]. Moreover, enhanced eryptosis could contribute to the anemia following excessive formation, treatment or intoxication with hemolysin Kanagawa [65], listeriolysin [66], PGE 2 [67], lipoxygenase inhibitor Bay-5884 [68], platelet activating factor [69], paclitaxel [70], methylglyoxal [71], chlorpromazine [72], amantadine [73], cyclosporine [34], curcumin [74], amyloid peptides [75], aluminium [34], lead [32], mercury [33] and copper ions [35]. …”

Staphylococcus aureus α-Toxin Induces Inflammatory Cytokines via Lysosomal Acid Sphingomyelinase and Ceramides

“…Ceramide molecules spontaneously aggregate and form small domains that fuse to larger ceramide-enriched membrane platforms that serve to re-organize and cluster receptors and signaling molecules [25, 26]. The generation of ceramide molecules within membranes also changes membrane properties and membrane fluidity [27-31]. The re-organization of receptors and associated signaling molecules mediates many of the cellular effects of ceramides [25].…”