Hemin-induced suicidal erythrocyte death.
Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion may cause excessive formation of hemin, which may in turn trigger hemolysis. A variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis is elicited by increased cytosolic Ca(2+) activity and by ceramide. The present study explored whether hemin stimulates eryptosis. Cell membrane scrambling was estimated from annexin V-binding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in fluorescence-activated cell sorter analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide formation from fluorescence-labeled antibody binding. Exposure to hemin (1-10 microM) within 48 h significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation. In conclusion, hemin stimulates suicidal cell death, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.
Gatidis
Sergios
S
Department of Physiology, University of Tübingen, Tübingen, Germany.
Föller
Michael
M
Lang
Florian
F
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001773:Blood Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D006427:Hemin / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism
D017304:Annexin A5; D002518:Ceramides; D010718:Phosphatidylserines; D006427:Hemin; D002118:Calcium