Citation

Mahmud H, Föller M, Lang F. Arch. Toxicol. 2009; 83(2): 107-113.

Affiliation

Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.

Copyright

(Copyright © 2009, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s00204-008-0338-2

PMID

18636241

Abstract

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 Ca(2+) concentration, ceramide and energy depletion. The present experiments explored, whether arsenic stimulates eryptosis. According to annexin V-binding, arsenic trioxide (7 muM) within 48 h significantly increased phosphatidylserine exposure of human erythrocytes without inducing hemolysis. According to forward scatter, arsenic trioxide (7 muM) significantly decreased cell volume. Moreover, Fluo3-fluorescence showed that arsenic (10 muM) significantly increased cytosolic Ca(2+) concentration. According to binding of respective fluorescent antibodies, arsenic trioxide (10 muM) significantly increased ceramide formation. Arsenic (10 muM) further lowered the intracellular ATP concentration. Removal of extracellular Ca(2+) or inhibition of the Ca(2+)-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 Ca(2+) concentration, by stimulating the formation of ceramide and by decreasing ATP availability.

Language: en