title: Effect of saponin on erythrocytes.
abstract: Saponins, naturally occurring glycosides and triterpene glycosides in plants, are considered useful in the prophylaxis and treatment of several disorders, including malignancy. The effect of these substances is partly attributable to induction of both apoptosis and necrosis. Saponin has previously been shown to trigger hemolysis. Erythrocytes may avoid hemolysis by entering programmed cell death or eryptosis, characterized by cell shrinkage and cell membrane scrambling, leading to phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase of cytosolic Ca(2+) activity ([Ca(2+)](i)). The present study explored, whether exposure of human erythrocytes to saponin modifies [Ca(2+)](i), ceramide formation, hemolysis, and eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, hemolysis from hemoglobin release, [Ca(2+)](i) from Fluo3-fluorescence, and ceramide utilizing specific antibodies. A 24 h exposure to saponin (15 µg/ml) resulted in a significant increase of annexin V binding and a significant stimulation of hemolysis. Saponin (15 µg/ml) further increased [Ca(2+)](i) and ceramide formation. Annexin V binding was significantly blunted but not abrogated in the nominal absence of extracellular Ca(2+). Saponin thus triggers cell membrane scrambling, an effect partially due to entry of extracellular Ca(2+) and ceramide formation.
authors.affiliation: Department of Physiology, Eberhard-Karls-University of Tuebingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Paola
authors.initials: P
authors.lastname: Modicano
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Majed
authors.initials: M
authors.lastname: Abed
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
chemical_list: D010718:Phosphatidylserines; D012503:Saponins; D002118:Calcium