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Ceramide in the regulation of eryptosis, the suicidal erythrocyte death

  • THE ROLE OF SPHINGOLIPIDS AND LIPID RAFTS IN DETERMINING CELL FATE
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Abstract

Similar to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, a suicidal death characterized by cell shrinkage and phospholipid scrambling of the cell membrane leading to phosphatidylserine exposure at the cell surface. As eryptotic erythrocytes are rapidly cleared from circulating blood, excessive eryptosis may lead to anemia. Moreover, eryptotic erythrocytes may adhere to the vascular wall and thus impede microcirculation. Stimulators of eryptosis include osmotic shock, oxidative stress and energy depletion. Mechanisms involved in the stimulation eryptosis include ceramide formation which may result from phospholipase A2 dependent formation of platelet activating factor (PAF) with PAF dependent stimulation of sphingomyelinases. Enhanced erythrocytic ceramide formation is observed in fever, sepsis, HUS, uremia, hepatic failure, and Wilson’s disease. Enhanced eryptosis is further observed in iron deficiency, phosphate depletion, dehydration, malignancy, malaria, sickle-cell anemia, beta-thalassemia and glucose-6-phosphate dehydrogenase-deficiency. Moreover, eryptosis is triggered by osmotic shock and a wide variety of xenobiotics, which are again partially effective by enhancing ceramide abundance. Ceramide formation is inhibited by high concentrations of urea. As shown in Wilson’s disease, pharmacological interference with ceramide formation may be a therapeutic option in the treatment of eryptosis inducing clinical disorders.

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Abbreviations

AE1:

Anion exchanger 1

AMP:

Adenosinmonophosphate

AMPK:

AMP activated kinase

GMP:

Cyclic guanosinmonophosphate

CXCL16:

CXC-Motiv-Chemokin 16

HUS:

Hemolytic uremic syndrome

G6PD:

Glucose-6-phosphate dehydrogenase

GLUT1:

Glucose transporter 1

PAF:

Platelet activating factor

PAK2:

p21-activated kinase 2

PDK1:

Phosphoinositide dependent kinase 1

TRPC6:

Transient receptor potential channel C6

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Acknowledgments

The authors acknowledge the meticulous preparation of the manuscript by Tanja Loch and Lejla Subasic. Their research has been supported by the Deutsche Forschungsgemeinschaft, Nr. La 315/4-3, La 315/6-1, La 315/13-1.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany

    Elisabeth Lang, Rosi Bissinger & Florian Lang

  2. Department of Molecular Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Erich Gulbins

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  1. Elisabeth Lang
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Correspondence to Florian Lang.

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Lang, E., Bissinger, R., Gulbins, E. et al. Ceramide in the regulation of eryptosis, the suicidal erythrocyte death. Apoptosis 20, 758–767 (2015). https://doi.org/10.1007/s10495-015-1094-4

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