The importance of Na + /H + exchanger for the generation of procoagulant activity by porcine blood platelets

Samson, J; Stelmach, Halina; Tomasiak, Marian

doi:10.1080/09537100120078395

Cited by 19 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently the most likely hypothesis could be that Na ϩ , as already described for Ca 2ϩ , acts by both inhibiting APLT and activating scramblase or other molecular complexes able to promote phospholipid transport. A role for intracellular Na ϩ has been proposed to explain other cellular processes such as reverse transport of dopamine (53), stress-activated protein kinase/c-Jun N-terminal kinase activation (54), P2X7-mediated membrane blebbing (36), and platelet procoagulant properties (49). In apoptosis, an early Na ϩ influx is involved in the control of cell shrinkage and activation of the apoptotic program (55).…”

Section: Atp Ec -Induced Ps Exposure Is Mediated By Namentioning

confidence: 99%

Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

Courageot

Lépine

Hours

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Extracellular ATP (ATP ec ), a possible effector in thymocyte selection, induces thymocyte death via purinoceptor activation. We show that ATP ec induced cell death by apoptosis, rather than lysis, and early phosphatidylserine (PS) exposure and phospholipid scrambling in a limited thymocyte population (35-40%). PS externalization resulted from the activation of the cationic channel P2X7 (formerly P2Z) receptor and was triggered in all thymocyte subsets although to different proportions in each one. Phospholipid movement was dependent on ATP ec -induced Ca 2؉ and/or Na ؉ influx. At physiological external Na ؉ concentration, without external Ca 2؉ , PS was exposed in all ATP ec -responsive cells. In contrast, without external Na ؉ , physiological external Ca 2؉ concentration promoted a submaximal response. Altogether these data show that Na ؉ influx plays a major role in the rapid PS exposure induced by P2X7 receptor activation in thymocytes. Extracellular ATP (ATP ec )1 induces thymocyte apoptosis and may play a role in thymocyte maturation (1-4). A major change of cell membrane during apoptosis, slightly preceding nuclear condensation (5), is the exposure on the exoplasmic cell surface of phosphatidylserine (PS) (6 -9), a phospholipid normally maintained on the inner membrane leaflet by the aminophospholipid translocase (APLT) (10). This process is associated with a general loss of the asymmetric distribution (scrambling) of all the other major phospholipids (6,7,9). The presence of specific PS receptors on macrophages potentially allows a rapid elimination of apoptotic cells by phagocytosis before their lysis (11). Rapid PS exposure and scrambling are generally observed after platelet activation or treatment of cells with a Ca 2ϩ ionophore, both conditions promoting a drastic and rapid rise in cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) (7). An involvement of Ca 2ϩ has been also reported in PS exposure during apoptosis (6,7,12). Ca 2ϩ acts by inhibiting APLT and by targeting scramblase (6, 7, 13) or other molecular complexes, which could contain phosphoinositides (14,15). Recent studies show that the rapid Ca 2ϩ -induced PS exposure is correlated with scramblase expression (16), in contrast to the delayed PS exposure associated with apoptosis (17, 18), in agreement with the involvement of other phospholipid transporters in apoptotic pathways.ATP ec is able to evoke physiological responses in a wide variety of cells and tissues. ATP is concentrated in cell cytosol and in exocytic vesicles, reaching 2-4 and 100 mM, respectively (19), and can be merely released from damaged cells, transported through carriers or channels, or secreted (19 -21). In the extracellular medium, its lifetime is very short due to its rapid degradation by ectonucleotidases and ecto-ATPases (19). ATP ec binds to distinct types of purinergic receptors classified into two subfamilies: metabotropic P2Y receptors coupled to Gprotein (P2Y1-6 and P2Y11) and ligand-gated ion channel P2X receptors (P2X1-7) (22). P2X7 receptor, previously designat...

show abstract

Section: Atp Ec -Induced Ps Exposure Is Mediated By Namentioning

confidence: 99%

Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

Courageot

Lépine

Hours

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Low concentrations of PMA (50-100 nM) were able to induce slow alkalinization in human platelets [16,17], but amplify recovery of pH after acidification induced by nigericin [16]. Higher concentrations (200 to 400 nM) were necessary to induce procoagulant activity [19] or serotonine secretion in porcine platelets [43]. Our data show that 50 nM PMA alone has no effect on PS externalization.…”

Section: Dependence Of Ps Exposure On Na + Influx Through Nhe Activationmentioning

confidence: 93%

“…The difference between the effect of Na + deprivation and EIPA on PS externalization could be linked to the inability of EIPA to reduce totally the increase in [Na] i even at 30 µM (the highest concentration that did not affect the resting platelet state) ( Table 2). Assuming that EIPA is a full inhibitor of NHE1 [19,20], this finding indicates that Na + influx via other pathways than NHE could be involved in this process.…”

Section: Dependence Of Ps Exposure On Na + Influx Through Nhe Activationmentioning

confidence: 97%

“…Monensin, a Na + /H + ionophore which mimics NHE function, has been shown previously to induce procoagulant activity in porcine platelets [19,20] and secretion in human platelets [43]. In human platelets, this ionophore raises the intracellular pH and Na + concentration within seconds [50].…”

Section: Dependence Of Ps Externalization On Na + Influx Ca 2+ Influmentioning

confidence: 99%

“…Recent observations suggest that Na + influx through NHE is necessary for the creation of procoagulant activity of porcine platelets [19] and of human platelets treated by desmopressin [20], and an enhanced platelet NHE exchanger activity found in type 2 diabetic patients is associated with elevated phospholipid-dependent procoagulant activity and increased risk of vascular damage [21]. Additionally, Na + influx resulting from P2X7 receptor activation by extracellular ATP was recently reported to induce rapid PS externalization in thymocytes [22].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Phospholipid Scramblase: When Phospholipid Asymmetry Goes Away

Bevers¹,

Williamson²

2011

Transmembrane Dynamics of Lipids

View full text Add to dashboard Cite

The importance of Na + /H + exchanger for the generation of procoagulant activity by porcine blood platelets

Cited by 19 publications

References 24 publications

Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

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

Phospholipid Scramblase: When Phospholipid Asymmetry Goes Away

Contact Info

Product

Resources

About