Suicidal death of erythrocytes due to selenium-compounds.
Selenium is an essential element incorporated into selenoproteins. Selenium deficiency may predispose to immune deficiency, mood disorders, and cancer. On the other hand, excessive environmental exposure to selenite may cause a variety of disorders including anemia. At least in theory, the anemia could result from accelerated suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by an increase in the cytosolic Ca(2+) concentration and by ceramide. The present experiments explored, whether high concentrations of selenite stimulate eryptosis. According to Fluo3 fluorescence, selenite (>or=200 microg/l sodium selenite) within 48 hours significantly increased the cytosolic Ca(2+) concentration in human erythrocytes. According to binding of selective fluorescent antibodies, selenite (>or= 200 microg/l) significantly increased ceramide formation. Annexin V-binding demonstrated that selenite (>or=200 microg/l) significantly increased phosphatidylserine exposure of erythrocytes. Forward scatter analysis further revealed that selenite (>or=200 microg/l) significantly decreased cell volume. In contrast to selenite, selenate failed to trigger eryptosis. In conclusion, selenite triggers suicidal erythrocyte death at least partially by increasing the cytosolic Ca(2+) concentration and by stimulating the formation of ceramide. The present study discloses novel cellular effects of this essential nutrient.
Sopjani
Mentor
M
Department of Physiology, University of Tübingen, Tübingen, Germany.
Föller
Michael
M
Gulbins
Erich
E
Lang
Florian
F
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects*; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D012542:Scattering, Radiation; D064586:Selenic Acid; D018036:Selenium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology
D002518:Ceramides; D010718:Phosphatidylserines; D018036:Selenium Compounds; D018038:Sodium Selenite; D064586:Selenic Acid; D002118:Calcium; D019803:Glutathione Disulfide