title: Enhanced Ca2+ entry, ceramide formation, and apoptotic death of erythrocytes triggered by plumbagin.
abstract: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, 1), a natural product from plants with potential anticancer potency, induces apoptosis. Mechanisms involved in 1-induced apoptosis include mitochondrial depolarization, inactivation of NF-κB, and altered expression of anti- and proapoptotic Bcl proteins. Similar to nucleated cells, erythrocytes may undergo suicidal death or eryptosis, which, like apoptosis, results in cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca(2+) activity ([Ca(2+)]i) and ceramide formation. The present study explored whether 1 stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo-3 fluorescence, and ceramide abundance utilizing antibodies. A 48 h exposure to 1 (2 μM) decreased forward scatter and increased annexin-V-binding significantly, events paralleled by increased [Ca(2+)]i and ceramide formation. Exposure to 1 was followed by a slight but significant increase of hemolysis. Removal of extracellular Ca(2+) slightly, but significantly blunted the effect of 1 (2 μM) on annexin-V-binding. The present observations demonstrate that 1 may trigger suicidal death of erythrocytes, cells devoid of mitochondria and nuclei.
authors.affiliation: Department of Physiology, University of Tuebingen , Gmelinstraße 5, 72076 Tuebingen, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Mohanad
authors.initials: M
authors.lastname: Zbidah
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000276:immunology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D024483:Vitamin K 3 / Q000378:metabolism; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D002518:Ceramides; D016328:NF-kappa B; D009285:Naphthoquinones; D010718:Phosphatidylserines; D014966:Xanthenes; C059715:Fluo-3; D024483:Vitamin K 3; D002118:Calcium; C014758:plumbagin