title: Therapeutic potential of manipulating suicidal erythrocyte death.
abstract: BACKGROUND
  Eryptosis, the suicidal erythrocyte death, is characterized by erythrocyte shrinkage and phosphatidylserine translocation to the erythrocyte surface. Eryptosis is triggered by cell stress such as energy depletion and oxidative stress, by Ca(2+)-entry, ceramide, caspases, calpain and/or altered activity of several kinases. Phosphatidylserine-exposing erythrocytes adhere to the vascular wall and may thus impede microcirculation. Eryptotic cells are further engulfed by phagocytes and thus rapidly cleared from circulation.
  
  
  METHODS
  Stimulation of eryptosis contributes to anemia of several clinical conditions such as metabolic syndrome, diabetes, malignancy, hepatic failure, heart failure, uremia, hemolytic uremic syndrome, sepsis, fever, dehydration, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency and Wilson's disease. On the other hand, eryptosis with subsequent clearance of infected erythrocytes in malaria may counteract parasitemia.
  
  
  CONCLUSIONS
  In theory, anemia due to excessive eryptosis could be alleviated by treatment with small molecules inhibiting eryptosis. In malaria, stimulators of eryptosis may accelerate death of infected erythrocytes and thus favorably influence the clinical course of the disease. Many small molecules inhibit or stimulate eryptosis. Several stimulators favorably influence murine malaria. Further preclinical and subsequent clinical studies are required to elucidate the therapeutic potential of stimulators or inhibitors of eryptosis.
authors.affiliation: University of Tübingen, Department of Physiology , Gmelinstr. 5, 72076 Tübingen , Germany +49 7071 29 72194 ; +49 7071 29 5618 ; florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D018384:Oxidative Stress / Q000502:physiology; D010586:Phagocytes / Q000378:metabolism
keywords: anemia; chronic kidney disease; diabetes; eryptosis; malaria; sickle cell disease; thrombosis