Inhibition of suicidal erythrocyte death by nitric oxide. Academic Article uri icon


  • 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.

published proceedings

  • Pflugers Arch

altmetric score

  • 3

author list (cited authors)

  • Nicolay, J. P., Liebig, G., Niemoeller, O. M., Koka, S., Ghashghaeinia, M., Wieder, T., ... Lang, F.

citation count

  • 59

complete list of authors

  • Nicolay, Jan P||Liebig, Gerd||Niemoeller, Olivier M||Koka, Saisudha||Ghashghaeinia, Mehrdad||Wieder, Thomas||Haendeler, Judith||Busse, Rudi||Lang, Florian

publication date

  • May 2008