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Open AccessArticle

Carmustine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

Department of Physiology, University of Tuebingen, Gmelinstr. 5, Tuebingen D-72076, Germany
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Toxins 2013, 5(4), 703-716; https://doi.org/10.3390/toxins5040703
Received: 20 February 2013 / Revised: 7 April 2013 / Accepted: 10 April 2013 / Published: 19 April 2013
The nitrosourea alkylating agent, carmustine, is used as chemotherapeutic drug in several malignancies. The substance triggers tumor cell apoptosis. Side effects of carmustine include myelotoxicity with anemia. At least in theory, anemia could partly be due to stimulation of eryptosis, the suicidal death of erythrocytes, characterized by cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i). The present study tested whether carmustine triggers eryptosis. To this end [Ca2+]i was estimated from Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding, and hemolysis from hemoglobin release. As a result a 48 h exposure to carmustine (≥25 µM) significantly increased [Ca2+]i, decreased forward scatter and increased annexin V binding. The effect on annexin V binding was significantly blunted in the absence of extracellular Ca2+. In conclusion, carmustine stimulates eryptosis at least partially by increasing cytosolic Ca2+ activity. View Full-Text
Keywords: phosphatidylserine; carmustine; calcium; cell volume; eryptosis phosphatidylserine; carmustine; calcium; cell volume; eryptosis
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Jilani, K.; Lang, F. Carmustine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane. Toxins 2013, 5, 703-716.

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