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Fluoxetine Induced Suicidal Erythrocyte Death
Department of Physiology, University of Tuebingen, Gmelinstr. 5, Tuebingen 72076, Germany
Zentrum für Klinische Transfusionsmedizin, Otfried-Müller-Straße 4/1, Tuebingen 72076, Germany
* Author to whom correspondence should be addressed.
Received: 23 May 2013; in revised form: 28 June 2013 / Accepted: 4 July 2013 / Published: 15 July 2013
Abstract: The antidepressant fluoxetine inhibits ceramide producing acid sphingomyelinase. Ceramide is in turn known to trigger eryptosis the suicidal death of erythrocytes characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Ceramide is effective through sensitizing the erythrocytes to the pro-eryptotic effect of increased cytosolic Ca2+ activity ([Ca2+]i). In nucleated cells, fluoxetine could either inhibit or stimulate suicidal death or apoptosis. The present study tested whether fluoxetine influences eryptosis. To this end cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, hemolysis from hemoglobin release and [Ca2+]i from Fluo-3 fluorescence intensity. As a result, a 48 h exposure of erythrocytes to fluoxetine (≥25 µM) significantly decreased forward scatter, increased annexin V binding and enhanced [Ca2+]i. The effect on annexin V binding was significantly blunted, but not abolished, in the absence of extracellular Ca2+. In conclusion, fluoxetine stimulates eryptosis, an effect at least in part due to increase of cytosolic Ca2+ activity.
Keywords: phosphatidylserine; fluoxetine; calcium; cell volume; eryptosis
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MDPI and ACS Style
Jilani, K.; Enkel, S.; Bissinger, R.; Almilaji, A.; Abed, M.; Lang, F. Fluoxetine Induced Suicidal Erythrocyte Death. Toxins 2013, 5, 1230-1243.
Jilani K, Enkel S, Bissinger R, Almilaji A, Abed M, Lang F. Fluoxetine Induced Suicidal Erythrocyte Death. Toxins. 2013; 5(7):1230-1243.
Jilani, Kashif; Enkel, Sigrid; Bissinger, Rosi; Almilaji, Ahmad; Abed, Majed; Lang, Florian. 2013. "Fluoxetine Induced Suicidal Erythrocyte Death." Toxins 5, no. 7: 1230-1243.