title: Stimulation of Eryptosis by Narasin.
abstract: OBJECTIVE
  Narasin, an ionophore used for the treatment of coccidiosis, has been shown to foster apoptosis of tumor cells. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by Ca2+ entry with subsequent increase of cytosolic Ca2+ activity ([Ca2+]i), and by ceramide. The present study explored, whether and how narasin induces eryptosis.
  
  
  METHODS
  Flow cytometry was employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific antibodies.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to narasin (10 and 25 ng/ml) significantly increased the percentage of annexin-V-binding cells. Forward scatter was decreased by 1 ng/ml narasin but not by higher narasin concentrations (10 and 25 ng/ml). Narasin significantly increased Fluo3-fluorescence (10 and 25 ng/ml) and slightly, but significantly increased ceramide abundance (25 ng/ml). The effect of narasin on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+.
  
  
  CONCLUSIONS
  Narasin triggers phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled and partially dependent on Ca2+ entry. Narasin further leads to cell shrinkage and slight increase of ceramide abundance.
authors.forename: Ghada
authors.initials: G
authors.lastname: Bouguerra
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Salem
authors.initials: S
authors.lastname: Abbès
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D000900:Anti-Bacterial Agents; D002518:Ceramides; D007477:Ions; D010718:Phosphatidylserines; D011714:Pyrans; D014966:Xanthenes; C059715:Fluo-3; C013612:narasin; D002118:Calcium