Home / FlashMed

FlashMed

Titolo The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death
Autore Mohamed Siyabeldin E. Ahmed, Henning Langer, Majed Abed, Jakob Voelkl, Florian Lang
Referenza Kidney Blood Press Res 2013; 37: 158-167
Contenuto

Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i). Erythrocytes could be sensitized to cytosolic Ca2+ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis.

Methods: Cell volume was estimated from forward scatter, phosphatidylserineexposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies.

Results: A 48 h exposure to acrolein (30 – 50 μM) did not significantly modify [Ca2+]i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 μM) induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca2+. Acrolein augmented the annexin-V-binding following treatment with Ca2+ ionophore ionomycin (1 μM).

Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca2+.

Data 10.01.2014
 
Maggiori informazioni   
Lista completa