Arsenic-induced suicidal erythrocyte death.
Environmental exposure to arsenic has been associated with anemia, which could result from suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase in cytosolic Ca2+ concentration, ceramide and energy depletion. The present experiments explored, whether arsenic stimulates eryptosis. According to annexin V-binding, arsenic trioxide (7 microM) within 48 h significantly increased phosphatidylserine exposure of human erythrocytes without inducing hemolysis. According to forward scatter, arsenic trioxide (7 microM) significantly decreased cell volume. Moreover, Fluo3-fluorescence showed that arsenic (10 microM) significantly increased cytosolic Ca2+ concentration. According to binding of respective fluorescent antibodies, arsenic trioxide (10 microM) significantly increased ceramide formation. Arsenic (10 microM) further lowered the intracellular ATP concentration. Removal of extracellular Ca2+ or inhibition of the Ca2+-permeable cation channels with amiloride blunted the effects of arsenic on annexin V-binding and cell shrinkage. In conclusion, arsenic triggers suicidal erythrocyte death by increasing cytosolic Ca2+ concentration, by stimulating the formation of ceramide and by decreasing ATP availability.
Mahmud
Hasan
H
Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
Föller
Michael
M
Lang
Florian
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D001151:Arsenic / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects*; D002518:Ceramides / Q000096:biosynthesis; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism
D002518:Ceramides; D010718:Phosphatidylserines; D000255:Adenosine Triphosphate; D001151:Arsenic; D002118:Calcium