title: Stimulation of erythrocyte cell membrane scrambling by gedunin.
abstract: OBJECTIVE
  Gedunin, an inhibitor of heat shock protein HSP90, triggers apoptosis of tumor cells and is thus effective against malignancy. Moreover, the drug has antimalarial potency. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored whether gedunin stimulates eryptosis.
  
  
  METHODS
  Forward scatter was determined to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to depict hemolysis, and Fluo3-fluorescence to quantify [Ca(2+)]i.
  
  
  RESULTS
  A 48 h exposure of human erythrocytes to gedunin significantly increased [Ca(2+)]i (12 µM), significantly decreased forward scatter (24 µM) and significantly increased annexin-V-binding (12 µM). The effect of gedunin (24 µM) on annexin-V-binding was virtually abrogated by removal of extracellular Ca(2+).
  
  
  CONCLUSIONS
  Gedunin stimulates suicidal erythrocyte death or eryptosis, an effect mainly if not exclusively due to stimulation of Ca(2+) entry.
authors: Department of Physiology, University of Tübingen, Germany.
authors: Adrian
authors: A
authors: Lupescu
authors: Rosi
authors: R
authors: Bissinger
authors: Jamshed
authors: J
authors: Warsi
authors: Kashif
authors: K
authors: Jilani
authors: Florian
authors: F
authors: Lang
mesh_terms: D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D036701:Limonins / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010718:Phosphatidylserines / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002518:Ceramides; D036701:Limonins; D010718:Phosphatidylserines; C106014:gedunin; D002118:Calcium