Stimulation of Suicidal Erythrocyte Death by PRIMA-1

Faggio, Caterina; Alzoubi, Kousi; Calabrò, Salvatrice; Läng, Florian

doi:10.1159/000369717

Cited by 61 publications

(17 citation statements)

References 104 publications

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“…Eryptosis is enhanced by erythrocyte age [48], a wide variety of anemia-causing xenobiotics and endogeneous substances [29,30,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] as well as several clinical disorders, such as iron deficiency [27], hepatic failure [69], chronic kidney disease [70], sepsis [71], malignancy [72] and Wilson's disease [73]. Eryptosis may further influence erythrocytes stored for transfusion [74].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival

Lang

Jilani

Bissinger

et al. 2015

Kidney Blood Press Res

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Background/Aims: Epidemiological evidence suggests that vitamin D deficiency is associated with anemia. The potent metabolite 1,25(OH)₂ vitamin D₃ [1,25(OH)₂D₃] activates various signaling cascades regulating a myriad of cellular functions including suicidal cell death or apoptosis. Suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Stimulation of eryptosis may limit lifespan of circulating erythrocytes and thus cause anemia. In the present study, we explored the effect of a high vitamin D diet (10,000 I.U. vitamin D for 14 days) in mice on eryptosis. Methods: Plasma concentrations of erythropoietin were estimated using an immunoassay kit, blood count using an electronic hematology particle counter, relative reticulocyte numbers using Retic-COUNT® reagent, PS exposure at the cell surface from annexin V binding, cell volume from forward scatter, and cytosolic Ca²⁺ ([Ca²⁺]_i) from Fluo3-fluorescence in FACS analysis. Results: Vitamin D treatment decreased mean corpuscular volume, reticulocyte count, and plasma erythropoietin levels. Vitamin D treatment slightly but significantly decreased forward scatter but did not significantly modify spontaneous PS exposure and [Ca²⁺]_i of freshly drawn erythrocytes. Vitamin D treatment augmented the stimulation of PS exposure and cell shrinkage following exposure to hyperosmotic shock (addition of 550 mM sucrose) or energy depletion (glucose removal) without significantly modifying [Ca²⁺]_i. Conclusions: The present observations point to a subtle effect of exogenous vitamin D supplementation on erythrocyte survival.

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Section: Discussionmentioning

confidence: 99%

Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival

Lang

Jilani

Bissinger

et al. 2015

Kidney Blood Press Res

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“…Translocation of PS from the inner to the outer membrane leaflet of RBCs is a typical sign of eryptosis (a term introduced by Lang [24]), defining the suicidal death of RBCs. A large variety of physiological parameters as well as substances have been described to induce eryptosis (e.g., [25][26][27][28][29][30][31]). …”

Section: Introductionmentioning

confidence: 99%

Measurements of Intracellular Ca2+ Content and Phosphatidylserine Exposure in Human Red Blood Cells: Methodological Issues

Wesseling

Wagner-Britz²,

Boukhdoud³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The increase of the intracellular Ca²⁺ content as well as the exposure of phosphatidylserine (PS) on the outer cell membrane surface after activation of red blood cells (RBCs) by lysophosphatidic acid (LPA) has been investigated by a variety of research groups. Carrying out experiments, which we described in several previous publications, we observed some discrepancies when comparing data obtained by different investigators within our research group and also between batches of LPA. In addition, we found differences comparing the results of double and single labelling experiments (for Ca²⁺ and PS). Furthermore, the results of PS exposure depended on the fluorescent dye used (annexin V-FITC versus annexin V alexa fluor® 647). Therefore, it seems necessary to investigate these methodological approaches in more detail to be able to quantify results and to compare data obtained by different research groups. Methods: The intracellular Ca²⁺ content and the PS exposure of RBCs separated from whole blood have been investigated after treatment with LPA (2.5 µM) obtained from three different companies (Sigma-Aldrich, Cayman Chemical Company, and Santa Cruz Biotechnology Inc.). Fluo-4 and x-rhod-1 have been used to detect intracellular Ca²⁺ content, annexin V alexa fluor® 647 and annexin V-FITC have been used for PS exposure measurements. Both parameters (Ca²⁺ content, PS exposure) were studied using flow cytometry and fluorescence microscopy. Results: The percentage of RBCs showing increased intracellular Ca²⁺ content as well as PS exposure changes significantly between different LPA manufacturers as well as on the condition of mixing of LPA with the RBC suspension. Furthermore, the percentage of RBCs showing PS exposure is reduced in double labelling compared to single labelling experiments and depends also on the fluorescent dye used. Finally, data on Ca²⁺ content are slightly affected whereas PS exposure data are not affected significantly by the measuring method (flow cytometry, fluorescence microscopy). Conclusion: The LPA batch used and the mixing procedure of LPA and the RBC suspension has to be taken into consideration when comparing results of intracellular Ca²⁺ content and PS exposure of RBCs after LPA activation. In addition, one should consider that the results of single and double labelling experiments might be different depending on the fluorescent dyes used.

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“…Mechanisms involved in the stimulation of apoptosis by reversine include inhibition of Akt/ mTORC1 signaling [88], caspase activation [5, 10, 22, 88], mitochondrial depolarization [22], autophagy [3, 10, 88] and mitotic catastrophe [20, 25, 27]. …”

Section: Discussionmentioning

confidence: 99%

“…The cell membrane scrambling is typically paralleled by cell shrinkage [34]. Triggers of eryptosis include oxidative stress [33], energy depletion [33], and exposure to a wide variety of xenobiotics [33, 35-88]. Cellular mechanisms involved include increase of cytosolic Ca 2+ activity ([Ca 2+ ] i ) [33], ceramide [89], G-protein Galphai2 [90], and several kinases including activated casein kinase 1a, Janus-activated kinase JAK3, protein kinase C, and p38 kinase [33], or inactivated AMP activated kinase AMPK, cGMP-dependent protein kinase, PAK2 kinase, mitogen and stress activated kinase MSK1/2 [91] and sorafenib/sunitinib sensitive kinases [33].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Suicidal Erythrocyte Death by Reversine

Jèmaà

Fezai

Läng³

2017

Cell Physiol Biochem

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Background/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect on apoptosis involves mitochondria and caspases. Erythrocytes are lacking mitochondria but express caspases and are, similar to apoptosis of nucleated cells, able to enter suicidal erythrocyte death or eryptosis. Stimulators of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), energy depletion and oxidative stress. The present study explored, whether reversine influences eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding and cell volume from forward scatter. Measurements were made without or with energy depletion (glucose deprivation for 48 hours), Ca²⁺ loading (30 minutes treatment with 1 µM Ca²⁺ ionophore ionomycin), or oxidative stress (15 min exposure to 0.3 mM tert-butylhydroperoxide). Results: A 48 hours exposure of human erythrocytes to reversine (1-10 µM) did not significantly modify the percentage of annexin-V-binding cells and forward scatter. Energy depletion, Ca²⁺ loading, and oxidative stress were each followed by profound and significant increase of the percentage annexin-V-binding erythrocytes and a significant decrease of forward scatter. The effects of each, Ca²⁺ loading, energy depletion and oxidative stress on annexin-V-binding were significantly blunted in the presence of reversine (1-10 µM). The effect of ionomycin, but not the effects of energy depletion and oxidative stress on forward scatter were again significantly blunted in the presence of reversine (≥1 µM]. Conclusions: Reversine is a powerful inhibitor of cell membrane scrambling following energy depletion, Ca²⁺ loading and oxidative stress.

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Stimulation of Suicidal Erythrocyte Death by PRIMA-1

Cited by 61 publications

References 104 publications

Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival

Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival

Measurements of Intracellular Ca2+ Content and Phosphatidylserine Exposure in Human Red Blood Cells: Methodological Issues

Inhibition of Suicidal Erythrocyte Death by Reversine

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