Zinc-induced suicidal erythrocyte death.
BACKGROUND
Zn(2+) stimulates secretory sphingomyelinase, which in turn produces ceramide, an important trigger of suicidal erythrocyte death or eryptosis. Eryptosis is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. As macrophages are equipped with PS receptors, they bind, engulf, and degrade PS-exposing cells.


OBJECTIVE
We examined whether Zn(2+) stimulates ceramide formation and PS exposure of erythrocytes and thus may be able to trigger suicidal erythrocyte death.


METHODS
In erythrocytes from healthy volunteers, PS exposure (Annexin V binding), cell volume (forward scatter), cytosolic Ca(2+) activity (Fluo3 fluorescence), and ceramide formation (anticeramide antibody) were determined by fluorescence-assisted cell sorting.


RESULTS
Exposure to Zn(2+) (> or = 25 micromol/L Zn(2+)) significantly increased annexin binding. The effect was paralleled by increase of cytosolic Ca(2+) activity (> or = 25 micromol/L Zn(2+)) and by ceramide formation (> or = 10 micromol/L Zn(2+)). Glucose depletion (24 h) similarly increased PS exposure, an effect significantly enhanced in the presence of Zn(2+) (> or = 10 micromol/L Zn(2+)).


CONCLUSIONS
Zn(2+) triggers suicidal erythrocyte death, an effect partially due to ceramide formation and an increase of cytosolic Ca(2+) activity.
Kiedaisch
Valentin
V
Department of Physiology, University of Tübingen, Tübingen, Germany.
Akel
Ahmad
A
Niemoeller
Olivier M
OM
Wieder
Thomas
T
Lang
Florian
F
D017304:Annexin A5 / Q000378:metabolism*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis*; D004912:Erythrocytes / Q000187:drug effects*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D010718:Phosphatidylserines / Q000494:pharmacology; D011485:Protein Binding; D015032:Zinc / Q000494:pharmacology*
D017304:Annexin A5; D002518:Ceramides; D010718:Phosphatidylserines; D005947:Glucose; D015032:Zinc; D002118:Calcium