Ceramide in suicidal death of erythrocytes.
The suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling resulting in phosphatidylserine exposure at the cell surface. Eryptosis is stimulated in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Moreover, eryptosis is elicited by osmotic shock, oxidative stress, energy depletion as well as a wide variety of endogenous mediators and xenobiotics. Excessive eryptosis is observed in erythrocytes lacking the cGMP-dependent protein kinase type I (cGKI) or the AMP-activated protein kinase AMPK. Inhibitors of eryptosis include erythropoietin, nitric oxide NO, catecholamines and high concentrations of urea. Eryptosis-triggering diseases and chemicals are partially effective by stimulating the formation of ceramide, which in turn fosters cell membrane scrambling. Accordingly, ceramide-induced eryptosis participates in the pathophysiology of several diseases and contributes to the effects of a large number of xenobiotics. The mechanisms underlying ceramide formation in erythrocytes are, however, still ill defined. In case of osmotic cell shrinkage, ceramide formation is apparently due to activation of phospholipase 2, leading to formation of platelet activating factor PAF and PAF-dependent stimulation of ceramide formation, which possibly involves acid sphingomyelinase. Additional experiments are needed to conclusively define the ceramide-generating enzyme and the ceramide-dependent cellular events eventually leading to suicidal erythrocyte death.
Lang
Florian
F
Department of Physiology, University of Tübingen, Tübingen, Germany. florian.lang@uni-tuebingen.de
Gulbins
Erich
E
Lang
Philipp A
PA
Zappulla
Donatella
D
Föller
Michael
M
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002518:Ceramides / Q000378:metabolism / Q000502:physiology*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015262:Xenobiotics / Q000494:pharmacology
D002518:Ceramides; D015262:Xenobiotics; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D002118:Calcium