scholarly journals Hydroxytyrosol Decreases Phosphatidylserine Exposure and Inhibits Suicidal Death Induced by Lysophosphatidic Acid in Human Erythrocytes

2019 ◽  
Vol 53 (6) ◽  
pp. 921-932
Keyword(s):  
Lysophosphatidic Acid ◽  
Human Erythrocytes ◽  
Phosphatidylserine Exposure ◽  
Suicidal Death

scholarly journals Stimulating Effect of Terfenadine on Erythrocyte Cell Membrane Scrambling

2016 ◽  
Vol 38 (4) ◽  
pp. 1425-1434 ◽  
Author(s):  
Elena Signoretto ◽  
Michela Castagna ◽  
Abdulla Al Mamun Bhuyan ◽  
Florian Lang
Keyword(s):  
Cell Membrane ◽  
Human Erythrocyte ◽  
Haemoglobin Concentration ◽  
Annexin V ◽  
Human Erythrocytes ◽  
Forward Scatter ◽  
Erythrocyte Surface ◽  
Suicidal Death ◽  
Phosphatidylserine Translocation ◽  
Surface Signaling

Background/Aims: The antihistaminic drug Terfenadine may trigger apoptosis of tumor cells, an effect unrelated to its effect on histamine receptors. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling triggering eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, and ceramide. The present study explored, whether Terfenadine is capable to trigger eryptosis. Methods: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence, and ceramide abundance at the human erythrocyte surface utilizing specific antibodies. Hemolysis was quantified from haemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Terfenadine (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells and triggered hemolysis without significantly modifying the average forward scatter. Terfenadine (7.5 µM) significantly increased Fluo3-fluorescence, but did not significantly modify DCF fluorescence or ceramide abundance. The effect of Terfenadine on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca2+. Exposure of human erythrocytes to Ca2+ ionophore ionomycin (1 µM, 15 min) triggered annexin-V-binding, an effect augmented by Terfenadine pretreatment (10 µM, 48 hours). Conclusions: Terfenadine triggers phospholipid scrambling of the human erythrocyte cell membrane, an effect in part due to entry of extracellular Ca2+ and in part due to sensitizing human erythrocyte cell membrane scrambling to Ca2+.

Lysophosphatidic acid opens a Ca++ channel in human erythrocytes

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2420-2425
Author(s):  
Lu Yang ◽  
Dina A. Andrews ◽  
Philip S. Low
Keyword(s):  
Lysophosphatidic Acid ◽  
Kinase Inhibitors ◽  
Membrane Integrity ◽  
Protein Kinase Inhibitors ◽  
Human Erythrocytes ◽  
Channel Blockers ◽  
Ca Channel ◽  
Active Population ◽  
Fresh Rbcs ◽  
The Impact

Lysophosphatidic acid (LPA) is a lipid-derived second messenger that mobilizes many cells of the circulatory and vascular systems to assist in thrombus development and wound healing. LPA, however, has not been tested on human erythrocytes, largely because erythrocytes are considered to be both biologically inert and inactive in intercellular communication. To test this presumption, we have examined the impact of LPA on signaling reactions within the human red blood cell (RBC). Using both 45Ca++ and a Ca++-sensitive fluorescent probe (Fluo-3), we demonstrated that LPA, but not phosphatidic acid or the closely related sphingosine-1–phosphate, stimulates the influx of micromolar quantities of extracellular Ca++ into fresh RBCs. This Ca++ influx was shown to be channel mediated rather than leak promoted because the influx was observed at LPA concentrations too low to perturb membrane integrity, it was inhibited by P-type but not L-type Ca++ channel blockers, it was inhibited by broad-specificity protein kinase inhibitors, and it was not induced by inactive analogues of LPA. Further characterization reveals that only approximately 25% of the RBCs participate in LPA-induced Ca++ entry and that within this active population, Ca++ gating occurs in an all-or-nothing manner. Because the stimulation of Ca++ uptake occurs at LPA concentrations (1-5 μmol/L) known to occur near a developing thrombus and because the internalized Ca++can potentially promote prothrombic properties in the stimulated RBCs, we conclude that RBCs are not insensitive to signals released from other cells.

scholarly journals Enhanced susceptibility to suicidal death of erythrocytes from transgenic mice overexpressing erythropoietin

2007 ◽  
Vol 293 (3) ◽  
pp. R1127-R1134 ◽  
Author(s):  
Michael Föller ◽  
Ravi S. Kasinathan ◽  
Saisudha Koka ◽  
Stephan M. Huber ◽  
Beat Schuler ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Transgenic Mice ◽  
Cell Volume ◽  
Cation Channels ◽  
Forward Scatter ◽  
Membrane Asymmetry ◽  
Phosphatidylserine Exposure ◽  
Suicidal Death ◽  
Osmotic Lysis ◽  
The Difference

Eryptosis, a suicidal death of mature erythrocytes, is characterized by decrease of cell volume, cell membrane blebbing, and breakdown of cell membrane asymmetry with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increased cytosolic Ca2+ activity, which could result from activation of Ca2+-permeable cation channels. Ca2+ triggers phosphatidylserine exposure and activates Ca2+-sensitive K+ channels, leading to cellular K+ loss and cell shrinkage. The cation channels and thus eryptosis are stimulated by Cl− removal and inhibited by erythropoietin. The present experiments explored eryptosis in transgenic mice overexpressing erythropoietin (tg6). Erythrocytes were drawn from tg6 mice and their wild-type littermates (WT). Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorting (FACS) analysis. The percentage of annexin binding was significantly larger and forward scatter significantly smaller in tg6 than in WT erythrocytes. Transgenic erythrocytes were significantly more resistant to osmotic lysis than WT erythrocytes. Cl− removal and exposure to the Ca2+ ionophore ionomycin (1 μM) increased annexin binding and decreased forward scatter, effects larger in tg6 than in WT erythrocytes. The K+ ionophore valinomycin (10 nM) triggered eryptosis in both tg6 and WT erythrocytes and abrogated differences between genotypes. An increase of extracellular K+ concentration to 125 mM blunted the difference between tg6 and WT erythrocytes. Fluo-3 fluorescence reflecting cytosolic Ca2+ activity was larger in tg6 than in WT erythrocytes. In conclusion, circulating erythrocytes from tg6 mice are sensitized to triggers of eryptosis but more resistant to osmotic lysis, properties at least partially due to enhanced Ca2+ entry and increased K+ channel activity.

scholarly journals Oxaliplatin Induced Suicidal Death of Human Erythrocytes

2015 ◽  
Vol 37 (6) ◽  
pp. 2393-2404 ◽  
Author(s):  
Antonella Fazio ◽  
Marilena Briglia ◽  
Caterina Faggio ◽  
Kousi Alzoubi ◽  
Florian Lang
Keyword(s):  
Cell Membrane ◽  
Annexin V ◽  
Human Erythrocytes ◽  
Cell Shrinkage ◽  
Forward Scatter ◽  
Erythrocyte Surface ◽  
Suicidal Death ◽  
Phosphatidylserine Translocation ◽  
Ros Formation ◽  
Binding Cell

Background/Aims: The alkylating drug oxaliplatin is widely used for chemotherapy of malignancy. Oxaliplatin is effective by inducing both, necrosis and apoptosis. Similar to necrosis or apoptosis of nucleated cells, erythrocytes may enter hemolysis, which is apparent from hemoglobin release or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress and/or Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether and how oxaliplatin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was quantified utilizing annexin-V-binding, cell volume estimated from forward scatter, hemolysis deduced from hemoglobin release, [Ca2+]i determined utilizing Fluo-3 fluorescence, and reactive oxygen species (ROS) abundance visualized using 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. Results: A 48 hours exposure of human erythrocytes to oxaliplatin (10 µg/ml) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, significantly increased Fluo-3 fluorescence, and significantly increased DCFDA fluorescence. The effect of oxaliplatin on annexin-V-binding and forward scatter was rather augmented by removal of extracellular Ca2+, but was significantly blunted in the presence of the antioxidant N-acetyl-cysteine (1 mM). Conclusions: Oxaliplatin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect partially dependent on ROS formation.

Inhibition of cation channels and suicidal death of human erythrocytes by zidovudine

Toxicology ◽  
2008 ◽  
Vol 253 (1-3) ◽  
pp. 62-69 ◽  
Author(s):  
Yuliya Kucherenko ◽  
Corinna Geiger ◽  
Ekaterina Shumilina ◽  
Michael Föller ◽  
Florian Lang
Keyword(s):  
Human Erythrocytes ◽  
Cation Channels ◽  
Suicidal Death

scholarly journals Antileukemic activity of sulfoxide nutraceutical allicin against THP-1 cells is associated with premature phosphatidylserine exposure in human erythrocytes

2020 ◽  
Vol 27 (12) ◽  
pp. 3376-3384
Author(s):  
Samar A. Sultan ◽  
Mohammed H. Khawaji ◽  
Jawaher Alsughayyir ◽  
Mohammad A. Alfhili ◽  
Hassan S. Alamri ◽  
...  
Keyword(s):  
Human Erythrocytes ◽  
Antileukemic Activity ◽  
Phosphatidylserine Exposure

scholarly journals Edelfosine Induced Suicidal Death of Human Erythrocytes

2015 ◽  
Vol 37 (6) ◽  
pp. 2221-2230 ◽  
Author(s):  
Marilena Briglia ◽  
Antonella Fazio ◽  
Elena Signoretto ◽  
Caterina Faggio ◽  
Florian Lang
Keyword(s):  
Cell Membrane ◽  
Annexin V ◽  
Human Erythrocytes ◽  
Cell Shrinkage ◽  
Forward Scatter ◽  
Erythrocyte Surface ◽  
Suicidal Death ◽  
Phosphatidylserine Translocation ◽  
Phospholipid Scrambling ◽  
Binding Cell

Background/Aims: The anti-inflammatory, anti-autoimmune, antiparasitic, and anti-viral ether phospholipid edelfosine (1-O-octadecyl-2-O-methylglycero-3-phosphocholine) stimulates apoptosis of tumor cells and is thus considered for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the cell membrane with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i) and oxidative stress. The present study explored, whether and how edelfosine induces eryptosis. Methods: Flow cytometry and photometry, respectively, were employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and abundance of reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. Results: A 6 hours exposure of human erythrocytes to edelfosine (5 µM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, and significantly increased Fluo3-fluorescence, but did not significantly modify DCFDA fluorescence. The effect of edelfosine on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Edelfosine triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry.

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