title: Carmustine-induced phosphatidylserine translocation in the erythrocyte membrane.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, Tuebingen D-72076, Germany. kashif_cbc@yahoo.com
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced; D017304:Annexin A5 / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D001771:Blood Banks; D020013:Calcium Signaling / Q000187:drug effects; D002330:Carmustine / Q000009:adverse effects / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D009994:Osmolar Concentration; D010718:Phosphatidylserines / Q000378:metabolism*; D013499:Surface Properties / Q000187:drug effects
chemical_list: D017304:Annexin A5; D018906:Antineoplastic Agents, Alkylating; D007202:Indicators and Reagents; D010718:Phosphatidylserines; D002330:Carmustine