title: Induction of suicidal erythrocyte death by novobiocin.
abstract: BACKGROUND
  Novobiocin, an aminocoumarin antibiotic, interferes with heat shock protein 90 and hypoxia inducible factor dependent gene expression and thus compromises cell survival. Similar to survival of nucleated cells, erythrocyte survival could be disrupted by eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phospholipd scrambling of the cell membrane with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The Ca(2+) sensitivity of phospholipid scrambling is enhanced by ceramide. The present study explored, whether novobiocin elicits eryptosis.
  
  
  METHODS
  [Ca(2+)]i was estimated from Fluo3-fluorescence, ceramide abundance utilizing fluorescent antibodies, cell volume from forward scatter, phosphatidylserine-exposure from annexin V binding.
  
  
  RESULTS
  A 48 hours exposure to novobiocin (500 µM) was followed by a significant increase of [Ca(2+)]i, decrease of forward scatter, increase of annexin-V-binding and enhanced ceramide formation. Removal of extracellular Ca(2+) virtually abrogated the increase of annexin-V-binding following novobiocin exposure.
  
  
  CONCLUSIONS
  Novobiocin stimulates eryptosis, an effect at least in part due to entry of extracellular Ca(2+) and formation of ceramide.
authors.affiliation: Department of Physiology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Tabea
authors.initials: T
authors.lastname: Herrmann
authors.forename: Gergely
authors.initials: G
authors.lastname: Oswald
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009675:Novobiocin / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D002518:Ceramides; D009675:Novobiocin; D002118:Calcium