Calcium Induces Phospholipid Redistribution and Microvesicle Release in Human Erythrocyte Membranes by Independent Pathways

Bucki, Robert; Bachelot‐Loza, Christilla; Zachowski, Alain; Giraud, Françoise; Sulpice, Jean‐Claude

doi:10.1021/bi9805238

Cited by 82 publications

(78 citation statements)

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“…Phospholipid scrambling and MP generation have been shown, although closely regulated, to proceed by independent pathways (Bucki et al, 1998). Human RBC contain protein kinase C (PKC), which mediates the phosphorylation of cytoskeletal proteins, such as band 4.1, 4.9 and, probably, adducin (Danilov & Cohen, 1989).…”

Section: Research Papermentioning

confidence: 99%

“…An ATP-requiring mechanism responsible for the specific translocation of aminophospholipids (PS and PE), aminophospholipid translocase, has been demonstrated (Seigneuret & Devaux, 1984). An increase of the intracellular Ca 2+ concentration in RBC is known to activate the scrambling of membrane phospholipids (Zhou et al, 1997;Bucki et al, 1998). Phospholipid scrambling plays a stimulatory role in MP Yukinori Kozuma, Yuka Sawahata, Yumi Takei, Shigeru Chiba and Haruhiko Ninomiya…”

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confidence: 99%

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Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

et al. 2011

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SummaryThrombosis in paroxysmal nocturnal haemoglobinuria (PNH) has been suggested to be due to several pathophysiological states: a suppressed fibrinolytic system, increased leucocyte‐derived tissue factor, complement (C′)‐mediated damage to platelets and endothelia, or increased platelet‐ and endothelium‐derived microparticles (MPs). Because haemolytic attack is often accompanied by thrombosis in PNH, we studied the role of C′‐induced release of MPs in the thrombogenesis of PNH. C′ activation induced procoagulant alteration in PNH red blood cells (RBC), when assessed by thrombin generation in the presence of C′‐activated PNH RBC, which was abolished by their subsequent treatment with annexin V. Significant amounts of procoagulant MPs, measured by phosphatidylserine‐binding prothrombinase activity, were released from PNH RBC in association with the formation of C5b‐9, but not significantly before C5b‐8. Generation of procoagulant, annexin V‐binding, MPs from C′‐activated RBC was studied also by flow cytometry. While phorbol 12‐myristate 13‐acetate, an activator of protein kinase C (PKC), induced the release of MPs from normal RBC as well as PNH RBC, C′‐induced release of MPs from PNH RBC was Ca2+‐independent and not associated with the activation of PKC, calpain or caspase. Procoagulant properties of MPs released from PNH RBC could contribute to the thrombogenesis of PNH.

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Section: Research Papermentioning

confidence: 99%

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confidence: 99%

Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

et al. 2011

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“…The influence of pH on the effect of A23187 would deserve to be investigated. Changes in pH can modulate PS exposure by several mechanisms: (1) a direct effect of an increase in the concentration of protons as suggested from the induction of the redistribution of phospholipid analogs in IOVs by acidification [8,9]; (2) an inhibition of the aminophospholipid translocase mediated by acidic intracellular pH [62] could contribute to PS externalization, as previously shown in apoptotic cells [63]; (3) pH variations could modulate the affinity of intracellular messengers such as Ca 2+ or Na + for their targets, which include scramblase or phosphoinositides [15,26,64,65]. Since NHE activation leads to a prolonged Na + influx coupled with alkalinization in response to platelet activation, only the latter hypothesis has to be considered in our conditions.…”

Section: Discussionmentioning

confidence: 99%

“…These data argue that the relationship between this protein and the scrambling activity observed in intact cells is uncertain. Other studies show that the increase in cytosolic Ca 2+ is not sufficient to stimulate plasma membrane phospholipid scrambling [11] and the hypothesis that scrambling could result from the formation of microvesicles [12] induced by Ca 2+ has been experimentally invalidated [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Involvement of the Na+/H+ exchanger in membrane phosphatidylserine exposure during human platelet activation

Bucki

Pastore

Giraud

et al. 2006

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Platelet membrane phosphatidylserine (PS) exposure that regulates the production of thrombin represents an important link between platelet activation and the coagulation cascade. Here, we have evaluated the involvement of the Na + /H + exchanger (NHE) in this process in human platelets. PS exposure induced in human platelets by thrombin, TRAP, collagen or TRAP+ collagen was abolished in a Na + -free medium. Inhibition of the Na + /H + exchanger (NHE) by 5-(N-Ethyl-N-Isopropyl) Amiloride (EIPA) reduced significantly PS exposure, whereas monensin or nigericin, which mimic or cause activation of NHE, respectively, reproduced the agonist effect. These data suggest a role for Na + influx through NHE activation in the mechanism of PS exposure. This newly identified pathway does not discount a role for Ca 2+ , whose cytosolic concentration varies together with that of Na + after agonist stimulation. Ca 2+ deprivation from the incubation medium only attenuated PS exposure induced by thrombin, measured from the uptake of FM1-43 (a marker of phospholipid scrambling independent of external Ca 2+ ). Surprisingly, removal of external Ca 2+ partially reduced FM1-43 uptake induced by A23187, known as a Ca 2+ ionophore. The residual effect can be attributed to an increase in [Na + ] i mediated by the ionophore due to a lack of its specificity. Finally, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), previously reported as a target for Ca 2+ in the induction of phospholipid scrambling, was involved in PS exposure through a regulation of NHE activity. All these results would indicate that the mechanism that results in PS exposure uses redundant pathways inextricably linked to the physiopathological requirements of this process.

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“…As a common principle, increasing intracellular levels of Ca 2+ result in increased secretion of microvesicles. 17,18 For example, erythrocytes can be stimulated with high levels of extracellular Ca 2+ in combination with a suitable ionophore. 19,20 In various human tumor cell lines, microvesicle production was increased at extracellular Ca 2+ concentrations up to 25 mM, but concentrations higher than 10 mM also decreased cell viability.…”

Section: Introductionmentioning

confidence: 99%

Exosome mimetics: a novel class of drug delivery systems

Kooijmans¹,

Vader²,

Dommelen³

et al. 2012

IJN

255

124

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Abstract:The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.

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Calcium Induces Phospholipid Redistribution and Microvesicle Release in Human Erythrocyte Membranes by Independent Pathways

Cited by 82 publications

References 48 publications

Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

Involvement of the Na+/H+ exchanger in membrane phosphatidylserine exposure during human platelet activation

Exosome mimetics: a novel class of drug delivery systems

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