title: Bile Acid-Induced Suicidal Erythrocyte Death.
abstract: OBJECTIVE
  In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially attributed to conjugated bilirubin. The present study explored, whether bile acids may stimulate eryptosis.
  
  
  METHODS
  Phosphatidylserine exposing erythrocytes have been identified utilizing annexin V binding, cell volume estimated from forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies.
  
  
  RESULTS
  The exposure of human erythrocytes to glycochenodesoxycholic (GCDC) and taurochenodesoxycholic (TCDC) acid was followed by a significant decrease of forward scatter and significant increase of Fluo-3 fluorescence, ceramide abundance as well as annexin V binding. The effect on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca2+.
  
  
  CONCLUSIONS
  Bile acids stimulate suicidal cell death, an effect paralleled by and in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in turn lead to accelerated clearance of circulating erythrocytes and, thus, may contribute to anemia in cholestatic patients.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.forename: Vitaly I
authors.initials: VI
authors.lastname: Pozdeev
authors.forename: Sergios
authors.initials: S
authors.lastname: Gatidis
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Ralf
authors.initials: R
authors.lastname: Kubitz
authors.forename: Diran
authors.initials: D
authors.lastname: Herebian
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism; D001647:Bile Acids and Salts / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D000072817:Eryptosis / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005999:Glycochenodeoxycholic Acid / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000633:toxicity; D014966:Xanthenes / Q000737:chemistry / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D001647:Bile Acids and Salts; D002518:Ceramides; D002756:Cholagogues and Choleretics; D003902:Detergents; D010718:Phosphatidylserines; D014966:Xanthenes; C059715:Fluo-3; D013655:Taurochenodeoxycholic Acid; D005999:Glycochenodeoxycholic Acid; D002118:Calcium