Osmotic shock-induced suicidal death of erythrocytes.
Osmotic shock triggers eryptosis, a suicidal death of erythrocytes characterized by cell shrinkage, cell membrane blebbing and phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. Eryptosis following osmotic shock is mediated by two distinct signalling pathways. On the one hand, osmotic shock stimulates a cyclooxygenase leading to formation of prostaglandin E2 and subsequent activation of Ca2+-permeable cation channels. On the other hand, osmotic shock activates a phospholipase A2 leading to release of platelet activating factor, which in turn activates a sphingomyelinase and thus stimulates the formation of ceramide. The increased cytosolic Ca2+ concentrations on the one hand and ceramide on the other trigger phospholipid scrambling of the cell membrane with the subsequent shift of phosphatidylserine from the inner to the outer cell membrane leaflet. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and further cell shrinkage. The cation channels are inhibited by Cl- anions, erythropoietin and dopamine. The sphingomyelinase is inhibited by high concentrations of urea. Thus, the high Cl- and urea concentrations in renal medulla presumably prevent the triggering of eryptosis despite hyperosmolarity. The mechanisms involved in eryptosis may not only affect the survival of erythrocytes but may be similarly operative in nucleated cells exposed to osmotic shock.
Lang
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Department of Physiology, University of Tübingen, Tübingen, Germany. florian.lang@uni-tuebingen.de
Lang
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Lang
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Huber
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Wieder
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D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D002518:Ceramides / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007473:Ion Channels; D009997:Osmotic Pressure; D010718:Phosphatidylserines / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D002412:Cations; D002518:Ceramides; D007473:Ion Channels; D010718:Phosphatidylserines; D010972:Platelet Activating Factor; D002118:Calcium