title: Triggering of Suicidal Erythrocyte Death by Psammaplin A.
abstract: OBJECTIVE
  Psammaplin A, a natural product isolated from marine sponges, triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. In analogy to apoptosis of nucleated tumor cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms stimulating eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study explored, whether Psammaplin A induces eryptosis and to possibly shed some light on the underlying mechanisms.
  
  
  METHODS
  Phosphatidylserine exposing erythrocytes were identified utilizing annexin-V-binding, cell volume was estimated from forward scatter, [Ca2+]i determined utilizing Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) quantified with DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface detected with specific antibodies.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to Psammaplin A (2-8 µg/ml) significantly decreased forward scatter and significantly increased the percentage of annexin-V-binding cells. Psammaplin A significantly increased Fluo3-fluorescence, the effect of Psammaplin A on annexin-V-binding and forward scatter was, however, not significantly blunted by removal of extracellular Ca2+. Psammaplin A significantly increased DCFDA fluorescence and ceramide abundance.
  
  
  CONCLUSIONS
  Psammaplin A triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled by increase of [Ca2+]i, induction of oxidative stress and enhanced appearance of ceramide.
authors: Departments of Cardiology, Vascular Medicine and Physiology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.
authors: Abdulla
authors: A
authors: Al Mamun Bhuyan
authors: Elena
authors: E
authors: Signoretto
authors: Florian
authors: F
authors: Lang
mesh_terms: D000814:Aniline Compounds; D017304:Annexin A5; D001688:Biological Products / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D000072817:Eryptosis / Q000187:drug effects*; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D001688:Biological Products; D002518:Ceramides; D004220:Disulfides; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014966:Xanthenes; C098378:psammaplin A; C029569:diacetyldichlorofluorescein; C059715:Fluo-3; D014443:Tyrosine; D002118:Calcium