Stimulation of erythrocyte ceramide formation by platelet-activating factor

Lang, Philipp A.; Kempe, Daniela S.; Tanneur, Valérie; Eisele, Kerstin; Klarl, Barbara A.; Myssina, Svetlana; Jendrossek, Verena; Ishii, Satoshi; Shimizu, Takao; Waidmann, Marc; Hessler, Gabriele; Huber, Stephan M.; Läng, Florian; Wieder, Thomas

doi:10.1242/jcs.01730

Cited by 142 publications

(134 citation statements)

References 51 publications

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“…PKC␣ translocation and serine phosphorylation of cellular proteins were determined by Western blot analysis essentially as described (38). After incubation, the erythrocytes were washed three times in PBS and centrifuged at 450 g for 5 min.…”

Section: C247mentioning

confidence: 99%

Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion

Klarl¹,

Lang²,

Kempe³

et al. 2006

American Journal of Physiology-Cell Physiology

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194

197

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depletion of erythrocytes leads to activation of Ca 2ϩ -permeable cation channels, Ca 2ϩ entry, activation of a Ca 2ϩ -sensitive erythrocyte scramblase, and subsequent exposure of phosphatidylserine at the erythrocyte surface. Ca 2ϩ entry into erythrocytes was previously shown to be stimulated by phorbol esters and to be inhibited by staurosporine and chelerythrine and is thus thought to be regulated by protein phosphorylation/dephosphorylation, presumably via protein kinase C (PKC) and the corresponding phosphoserine/threonine phosphatases. The present experiments explored whether PKC could contribute to effects of energy depletion on erythrocyte phosphatidylserine exposure and cell volume. Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorter analysis. Removal of extracellular glucose led to depletion of cellular ATP, stimulated PKC activity, led to translocation of PKC␣, enhanced serine phosphorylation of membrane proteins, decreased cell volume, and increased annexin binding, the latter effect being blunted but not abolished in the presence of 1 M staurosporine or 50 nM calphostin C. The PKC stimulator phorbol-12-myristate-13-acetate (3 M) and the phosphatase inhibitor okadaic acid (1-10 M) mimicked the effect of glucose depletion and similarly led to translocation of PKC␣ and enhanced serine phosphorylation, increased annexin binding, and decreased forward scatter, the latter effects being abrogated by PKC inhibitor staurosporine (1 M). Fluo-3 fluorescence measurements revealed that okadaic acid also enhanced erythrocyte Ca 2ϩ activity. The present observations suggest that protein phosphorylation and dephosphorylation via PKC and the corresponding protein phosphatases contribute to phosphatidylserine exposure and cell shrinkage after energy depletion. cell volume; eryptosis; calcium; okadaic acid; staurosporine AS SHOWN RECENTLY, erythrocytes exposed to oxidative stress, osmotic shock, or glucose depletion activate a Ca 2ϩ -permeable cation channel (22,29,30,32)

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Section: C247mentioning

confidence: 99%

Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion

Klarl¹,

Lang²,

Kempe³

et al. 2006

American Journal of Physiology-Cell Physiology

Self Cite

194

197

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“…Complete protection of PAF-induced lung injury was obtained by a combined inhibition of the acid sphingomyelinase and the cyclooxygenase, suggesting that PAF employs two independent pathways to trigger pulmonary edema. In addition, PAF has been recently shown to trigger ceramide in human erythrocytes, leading to phosphatidylserine exposure on the surface of these cells (98). The exposure of this lipid may result in an increased phagocytosis of those erythrocytes and, finally, anemia.…”

Section: Ceramide-enriched Membrane Platforms In Infectious Biologymentioning

confidence: 99%

Physiological and pathophysiological aspects of ceramide

Gulbins

Li²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

212

172

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Activation of cells by receptor-and nonreceptor-mediated stimuli not only requires a change in the activity of signaling proteins but also requires a reorganization of the topology of the signalosom in the cell. The cell membrane contains distinct domains, rafts that serve the spatial organization of signaling molecules in the cell. Many receptors or stress stimuli transform rafts by the generation of ceramide. These stimuli activate the acid sphingomyelinase and induce a translocation of this enzyme onto the extracellular leaflet of the cell membrane. Surface acid sphingomyelinase generates ceramide that serves to fuse small rafts and to form large ceramide-enriched membrane platforms. These platforms cluster receptor molecules, recruit intracellular signaling molecules to aggregated receptors, and seem to exclude inhibitory signaling factors. Thus ceramide-enriched membrane platforms do not seem to be part of a specific signaling pathway but may facilitate and amplify the specific signaling elicited by the cognate stimulus. This general function may enable these membrane domains to be critically involved in the induction of apoptosis by death receptors and stress stimuli, bacterial and viral infections of mammalian cells, and the regulation of cardiovascular functions. signal transduction; acid sphingomyelinase; rafts; membrane platforms RECEPTOR AGGREGATION/CLUSTERINGIn recent years, the receptor-mediated activation of cells and signal transduction in cells has evolved to be determined by at least two principles: 1) receptors regulate the activity of enzymes, and 2) receptor molecules and intracellular signaling molecules are reorganized on stimulation. These two principles, i.e., activation/inactivation and a spatial reorganization of the cellular signalosom, determine the response of the cell to a stimulus. Many receptor molecules aggregate or cluster on stimulation; i.e., they are concentrated in a rather small area of the cell membrane, resulting in a very high density of the receptor molecules. Aggregation/clustering of cell surface receptors on binding their cognate ligands has been observed for many receptors, including the antigenic T cell receptor (TCR)-CD3 complex (19), the antigenic B cell receptor (62), the EGF receptor (3), CD40 (57), CD95 (11, 56), DR5 (C. Dumitru and E. Gulbins, unpublished observations), TNF (122), Fc␥RII (1), L-selectin (87), and integrins or leukoocyte function-associated antigen (LFA)-1 (136), to name a few. Clustering of receptor molecules correlates with a reassembly of intracellular signaling molecules. For instance, activation of the TCR-CD3 complex or the CD95 receptor results in an intracellular reorganization of the topology of CD4, Lck, Zap70, Ras, Rac-1, F-actin, and PKC (for comprehensive reviews, see Refs. 15,96), which are key molecules in the transmission of signals via the TCR-CD3 complex, or of FADD, caspase 8, and caspase 3, central mediators of CD95-induced apoptosis (for a recent review, see Ref. 112). Although it is widely accepted that these receptors cl...

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“…It further stimulates phospholipid scrambling of the cell membrane (4,13,33). Erythrocytes may be sensitized to the scrambling effect of Ca 2ϩ by ceramide (31,34), which is generated by a sphingomyelinase (38). 1 Phosphatidylserine exposure on erythrocytes provides a site for the assembly of coagulant enzymes, leading to thrombin generation and clotting (15).…”

mentioning

confidence: 99%

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

Borst

Abed²,

Alesutan³

et al. 2012

American Journal of Physiology-Cell Physiology

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222

215

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Suicidal death of erythrocytes, or eryptosis, is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca2+activity, which may result from treatment with the Ca2+ionophore ionomycin or from energy depletion by removal of glucose. The present study tested the hypothesis that phosphatidylserine exposure at the erythrocyte surface fosters adherence to endothelial cells of the vascular wall under flow conditions at arterial shear rates and that binding of eryptotic cells to endothelial cells is mediated by the transmembrane CXC chemokine ligand 16 (CXCL16). To this end, human erythrocytes were exposed to energy depletion (for 48 h) or treated with the Ca2+ionophore ionomycin (1 μM for 30 min). Phosphatidylserine exposure was quantified utilizing annexin-V binding, cell volume was estimated from forward scatter in FACS analysis, and erythrocyte adhesion to human vascular endothelial cells (HUVEC) was determined in a flow chamber model. As a result, both, ionomycin and glucose depletion, triggered eryptosis and enhanced the percentage of erythrocytes adhering to HUVEC under flow conditions at arterial shear rates. The adhesion was significantly blunted in the presence of erythrocyte phosphatidylserine-coating annexin-V (5 μl/ml), of a neutralizing antibody against endothelial CXCL16 (4 μg/ml), and following silencing of endothelial CXCL16 with small interfering RNA. The present observations demonstrate that eryptotic erythrocytes adhere to endothelial cells of the vascular wall in part by interaction of phosphatidylserine exposed at the erythrocyte surface with endothelial CXCL16.

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Stimulation of erythrocyte ceramide formation by platelet-activating factor

Cited by 142 publications

References 51 publications

Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion

Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion

Physiological and pathophysiological aspects of ceramide

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

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