Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Barvitenko, Nadezhda; Adragna, Norma C.; Weber, Roy E.

doi:10.1159/000083634

Cited by 135 publications

(108 citation statements)

References 211 publications

(242 reference statements)

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“…Scrambling of the cell membrane is further enhanced by ceramide, which is generated by a sphingomyelinase, at least following osmotic shock [15]. In analogy to senescent [11,[16][17][18] or neocytolytic [19] erythrocytes, eryptotic erythrocytes [11] are engulfed by macrophages [20] equipped with receptors specific for phosphatidylserine [21]. Thus, eryptotic erythrocytes are rapidly cleared from circulating blood [22].…”

Section: +mentioning

confidence: 99%

Amyloid Induced Suicidal Erythrocyte Death

Nicolay

Gatz

Liebig

et al. 2007

Cell Physiol Biochem

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Amyloid peptides are known to induce apoptosis in a wide variety of cells. Erythrocytes may similarly undergo suicidal death or eryptosis, which is characterized by scrambling of the cell membrane with subsequent exposure of phosphatidylserine (PS) at the cell surface. Eryptosis is triggered by increase of cytosolic Ca²⁺ activity and by activation of acid sphingomyelinase with subsequent formation of ceramide. Triggers of eryptosis include energy depletion and isosmotic cell shrinkage (replacement of extracellular Cl^- by impermeable gluconate for 24 h). The present study explored whether amyloid peptide Aβ _1-42 could trigger eryptosis and to possibly identify underlying mechanisms. Erythrocytes from healthy volunteers were exposed to amyloid and PS-exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca²⁺ activity (Fluo3 fluorescence) and ceramide formation (anti-ceramide antibody) were determined by FACS analysis. Exposure of erythrocytes to the amyloid peptide Aβ _1-42 (? 0.5 µM) for 24 h significantly triggered annexin V binding, an effect mimicked to a lesser extent by the amyloid peptide Aβ _1-40 (1 µM). Aβ _1-42 (? 1.0 µM) further significantly decreased forward scatter of erythrocytes. The effect of Aβ _1-42 (? 0.5 µM) on erythrocyte annexin V binding was paralleled by formation of ceramide but not by significant increase of cytosolic Ca²⁺ activity. The presence of Aβ _1-42 further significantly enhanced the eryptosis following Cl^- depletion but not of glucose depletion for 24 hours. The present observations disclose a novel action of Aβ _1-42, which may well contribute to the pathophysiological effects of amyloid peptides, such as vascular complications in Alzheimer''s disease.

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Section: +mentioning

confidence: 99%

Amyloid Induced Suicidal Erythrocyte Death

Nicolay

Gatz

Liebig

et al. 2007

Cell Physiol Biochem

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“…The term "eryptosis" has been coined to describe the suicidal death of erythrocytes characterized by decrease of forward scatter and phosphatidylserine exposure (43). Similar to erythrocyte senescence (6,13,43,70), eryptosis leads to accelerated clearance of circulating erythrocytes (40). Ca 2ϩ may enter erythrocytes through Ca 2ϩ -permeable cation channels (27,38), which are activated following osmotic shock by increase of extracellular osmolarity, oxidative stress by addition of t-butylhydroxyperoxide, and energy depletion by removal of extracellular glucose (42).…”

mentioning

confidence: 99%

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

Föller¹,

Kasinathan²,

Koka³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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“…The reticuloendothelial system involves the mononuclear phagocytic cells primarily in the spleen, and also in the liver and lymph nodes. The processes responsible for the actual triggering of the removal have been extensively studied (5,6,13,88).…”

Section: The Removal Of Rbcs From the Circulationmentioning

confidence: 99%

Hemoglobin Redox Reactions and Red Blood Cell Aging

Rifkind

Nagababu

2013

Antioxidants & Redox Signaling

132

112

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Significance: The physiological mechanism(s) for recognition and removal of red blood cells (RBCs) from circulation after 120 days of its lifespan is not fully understood. Many of the processes thought to be associated with the removal of RBCs involve oxidative stress. We have focused on hemoglobin (Hb) redox reactions, which is the major source of RBC oxidative stress. Recent Advances: The importance of Hb redox reactions have been shown to originate in large parts from the continuous slow autoxidation of Hb producing superoxide and its dramatic increase under hypoxic conditions. In addition, oxidative stress has been shown to be associated with redox reactions that originate from Hb reactions with nitrite and nitric oxide (NO) and the resultant formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation. Critical Issues: The interaction of Hb, particularly under hypoxic conditions with band 3 of the RBC membrane is critical for the generating the RBC membrane changes that trigger the removal of cells from circulation. These changes include exposure of antigenic sites, increased calcium leakage into the RBC, and the resultant leakage of potassium out of the RBC causing cell shrinkage and impaired deformability. Future Directions: The need to understand the oxidative damage to specific membrane proteins that result from redox reactions occurring when Hb is bound to the membrane. Proteomic studies that can pinpoint the specific proteins damaged under different conditions will help elucidate the cellular aging processes that result in cells being removed from circulation. Antioxid. Redox Signal. 18, 2274-2283.

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Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Cited by 135 publications

References 211 publications

Amyloid Induced Suicidal Erythrocyte Death

Amyloid Induced Suicidal Erythrocyte Death

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

Hemoglobin Redox Reactions and Red Blood Cell Aging

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