Calcium homeostasis in red blood cells of dialysis patients in dependence of erythropoietin treatment

Wang, Jue; Bentum, Kai van; Sester, Urban; Kaestner, Lars

doi:10.3389/fphys.2014.00016

Cited by 12 publications

(17 citation statements)

References 32 publications

(36 reference statements)

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“…However, 5 nM Epo was sufficient to inhibit the Ca 2+ signals induced by 0.1 nM PGE 2 . These data confirm the observation of a decreased PGE 2 -induced Ca 2+ response in Epo treated patients [12]. Because these results were in contradiction with what was reported for murine and human primary erythroblasts and erythroid cell lines [5,6], we performed the same experiments with RBCs from wild type mice.…”

Section: Resultscontrasting

confidence: 53%

“…In a previous investigation PGE 2 -stimulated Ca 2+ entry in Epo treated patients was smaller compared to not Epo treated patients [12]. In this study the modulation of erythropoiesis could have caused the change in Ca 2+ influx.…”

Section: Introductionmentioning

confidence: 75%

“…The abundance of transient receptor potential channels of canonical type (TRPC channels) in primary erythroblasts, erythroid cell lines and RBCs [4][5][6][7][8] was associated with an increase in intracellular Ca 2+ upon stimulation with Erythropoietin (Epo) [5,6]. Although the activity-regulation of the different TRPC isoforms can be complex [9,10], two independent studies on Epo-treated patients revealed diminished basal Ca 2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet that may be considered secondary to decreased intraerythrocytic Ca 2+ levels [11,12]. Furthermore, stimulation of RBCs with Prostaglandin E 2 (PGE 2 ) was associated with electrogenic Ca 2+ influx [13,14] and was considered as mediated by a TRPC channel [15].…”

Section: Introductionmentioning

confidence: 99%

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Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

Danielczok

Hertz

Ruppenthal

et al. 2017

Cell Physiol Biochem

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Background: Cation channels play an essential role in red blood cells (RBCs) ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels). The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca 2+ upon stimulation with Erythropoietin (Epo). In contrast two independent studies on Epo-treated patients revealed diminished basal Ca 2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E 2 (PGE 2 ) and recorded the intracellular Ca 2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE 2 regulation of the Ca 2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca 2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca 2+ fluxes but inhibits the PGE 2 -induced Ca 2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca 2+ entry activated by Epo whereas PGE 2 leads to a TRPC independent Ca 2+ entry.

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Section: Resultscontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

Danielczok

Hertz

Ruppenthal

et al. 2017

Cell Physiol Biochem

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“…Basal Ca 2+ -related fluorescence was measured as described before 49 . To evaluate the cellular distribution, confocal images of Fluo-4 loaded RBCs were recorded on a TCS SP5 (Leica, Mannheim, Germany) 50 .…”

Section: Methodsmentioning

confidence: 99%

‘Gardos Channelopathy’: a variant of hereditary Stomatocytosis with complex molecular regulation

Fermo

Bogdanova

Petkova-Kirova

et al. 2017

Sci Rep

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104

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The Gardos channel is a Ca2+ sensitive, K+ selective channel present in several tissues including RBCs, where it is involved in cell volume regulation. Recently, mutations at two different aminoacid residues in KCNN4 have been reported in patients with hereditary xerocytosis. We identified by whole exome sequencing a new family with two members affected by chronic hemolytic anemia carrying mutation R352H in the KCNN4 gene. No additional mutations in genes encoding for RBCs cytoskeletal, membrane or channel proteins were detected. We performed functional studies on patients’ RBCs to evaluate the effects of R352H mutation on the cellular properties and eventually on the clinical phenotype. Gardos channel hyperactivation was demonstrated in circulating erythrocytes and erythroblasts differentiated ex-vivo from peripheral CD34+ cells. Pathological alterations in the function of multiple ion transport systems were observed, suggesting the presence of compensatory effects ultimately preventing cellular dehydration in patient’s RBCs; moreover, flow cytometry and confocal fluorescence live-cell imaging showed Ca2+ overload in the RBCs of both patients and hypersensitivity of Ca2+ uptake by RBCs to swelling. Altogether these findings suggest that the ‘Gardos channelopathy’ is a complex pathology, to some extent different from the common hereditary xerocytosis.

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“…In each case one or multiple markers of senescence appear prematurely. Those include excessive oxidative stress (Mohanty et al, 2014), excessive cation leak with the following dehydration (Wang et al, 2014), decrease in RBC size and loss of RBC membrane through vesiculation (Alaarg et al, 2013), metabolic abnormalities (Vives-Corrons et al, 2013), or following autoimmune diseases (Lutz and Bogdanova, 2013). Blood storage damages RBCs facilitating aging.…”

mentioning

confidence: 99%

Regulation of red cell life-span, erythropoiesis, senescence and clearance

2014

Frontiers Research Topics

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Calcium homeostasis in red blood cells of dialysis patients in dependence of erythropoietin treatment

Cited by 12 publications

References 32 publications

Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

‘Gardos Channelopathy’: a variant of hereditary Stomatocytosis with complex molecular regulation

Regulation of red cell life-span, erythropoiesis, senescence and clearance

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