title: Embelin-Induced Phosphatidylserine Translocation in the Erythrocyte Cell Membrane.
abstract: OBJECTIVE
  The antihelminthic, contraceptive, anti-inflammatory and anticancer phytochemical embelin is at least in part effective against malignancy by inducing suicidal death or apoptosis of tumor cells. Erythrocytes are similarly able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca(2+)-activity ([Ca2+]i), ceramide formation, oxidative stress as well as activation of p38 kinase and protein kinase C (PKC). The present study tested, whether and how embelin induces eryptosis.
  
  
  METHODS
  Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to embelin (≥25 µM) significantly increased the percentage of annexin-V-binding cells and hemolysis. Embelin did not significantly modify [Ca2+]i. The effect of embelin on annexin-V-binding was not blunted by removal of extracellular Ca2+, by p38 kinase inhibitor SB203580 (2 µM) or by PKC inhibitor staurosporine (1 µM). Embelin did, however, significantly increase the ceramide abundance.
  
  
  CONCLUSIONS
  Embelin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect involving ceramide formation.
authors.forename: Ghada
authors.initials: G
authors.lastname: Bouguerra
authors.forename: Omar
authors.initials: O
authors.lastname: Aljanadi
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; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D016227:Benzoquinones; D002518:Ceramides; D007093:Imidazoles; D010718:Phosphatidylserines; D011725:Pyridines; D017382:Reactive Oxygen Species; D014966:Xanthenes; C059715:Fluo-3; D019311:Staurosporine; C093642:SB 203580; C010945:embelin; D002118:Calcium