Using a fast quantitative T2* magnetic resonance imaging technique, it was possible to gain insights into the iron metabolism of a healthy cohort. Gender- and age-related differences concerning T2* and serum ferritin levels were found in the liver and spleen, but not in the pancreas.

Nitric oxide (NO) is known to counteract apoptosis by S-nitrosylation of protein thiol groups. NO is generated and stored in erythrocytes, which may undergo eryptosis, a suicidal cell death similar to apoptosis of nucleated cells. Eryptosis is triggered by increased cytosolic Ca2+ activity and/or ceramide and characterized by cell shrinkage and phosphatidylserine exposure at the cell surface. The present study explored whether nitric oxide could interfere with the machinery underlying eryptosis. To this end, erythrocyte phosphatidylserine exposure (annexin V-binding) and cell volume (forward scatter) were determined by flow cytometry. The Ca2+ ionophore ionomycin (0.1 microM) increased cytosolic Ca2+ activity, triggered annexin binding, and decreased forward scatter. The annexin binding and decrease of forward scatter but not the increase of cytosolic Ca2+ activity were reversed by the NO-donor nitroprusside (1 microM) and papanonoate (100 microM). Higher concentrations of nitroprusside (0.1 and 1 mM) stimulated eryptosis. Glucose depletion, exposure to C6-ceramide (3 microM), hypertonic (addition of 550 mM sucrose), and isotonic (replacement of Cl- with gluconate) cell shrinkage all triggered annexin V binding, effects all reversed by nitroprusside (1 microM). Dibutyryl-cGMP (1 mM) blunted the ionomycin- but not the ceramide-induced annexin V binding. Ionomycin decreased protein nitrosylation and thioredoxin activity, effects reversed by the NO-donor papanonoate. Clearance of erythrocytes from circulating blood was significantly faster in eNOS knockout mice than in their wild-type littermates. In conclusion, nitric oxide participates in the regulation of erythrocyte survival, an effect partially mimicked by cGMP and paralleled by alterations of protein nitrosylation and thioredoxin activity.

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.

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