Stimulation of eryptosis by aluminium ions.
Aluminium salts are utilized to impede intestinal phosphate absorption in chronic renal failure. Toxic side effects include anemia, which could result from impaired formation or accelerated clearance of circulating erythrocytes. Erythrocytes may be cleared secondary to suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine (PS) at the erythrocyte surface. As macrophages are equipped with PS receptors, they bind, engulf and degrade PS-exposing cells. The present experiments have been performed to explore whether Al(3+) ions trigger eryptosis. The PS exposure was estimated from annexin binding and cell volume from forward scatter in FACS analysis. Exposure to Al(3+) ions (> or =10 microM Al(3+) for 24 h) indeed significantly increased annexin binding, an effect paralleled by decrease of forward scatter at higher concentrations (> or =30 microM Al(3+)). According to Fluo3 fluorescence Al(3+) ions (> or =30 microM for 3 h) increased cytosolic Ca(2+) activity. Al(3+) ions (> or =10 microM for 24 h) further decreased cytosolic ATP concentrations. Energy depletion by removal of glucose similarly triggered annexin binding, an effect not further enhanced by Al(3+) ions. The eryptosis was paralleled by release of hemoglobin, pointing to loss of cell membrane integrity. In conclusion, Al(3+) ions decrease cytosolic ATP leading to activation of Ca(2+)-permeable cation channels, Ca(2+) entry, stimulation of cell membrane scrambling and cell shrinkage. Moreover, Al(3+) ions lead to loss of cellular hemoglobin, a feature of hemolysis. Both effects are expected to decrease the life span of circulating erythrocytes and presumably contribute to the development of anemia during Al(3+) intoxication.
Niemoeller
Olivier M
OM
Department of Physiology, University of Tübingen, Germany.
Kiedaisch
Valentin
V
Dreischer
Peter
P
Wieder
Thomas
T
Lang
Florian
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002712:Chlorides; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D004905:Erythrocyte Aging / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding
D017607:Aluminum Compounds; D017304:Annexin A5; D002712:Chlorides; D006454:Hemoglobins; D010718:Phosphatidylserines; D000077410:Aluminum Chloride; D000255:Adenosine Triphosphate; D000535:Aluminum; D002118:Calcium