Enhanced suicidal erythrocyte death in acute cardiac failure

Attanasio, Philipp; Bissinger, Rosi; Haverkamp, Wilhelm; Pieske, Burkert; Wutzler, Alexander; Läng, Florian

doi:10.1111/eci.12555

Cited by 26 publications

(27 citation statements)

References 62 publications

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“…In a study by Attanasio et al ., the percentage of PS‐exposing erythrocytes was significantly higher in HF patients (1.8 ± 0.1%) as compared to the healthy control group (1.2 ± 0.2%). The increased eryptosis in these patients was accompanied by increased production of ROS , which are known to be enhanced in HF . Another study in five patients and a rat model suffering from HF provides further evidence that eryptosis may be a possible source contributing to anemia in that disease that has been missed out so far .…”

Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 71%

“…Recent evidence suggests that enhanced death of erythrocytes contributes to anemia in HF . In a study by Attanasio et al ., the percentage of PS‐exposing erythrocytes was significantly higher in HF patients (1.8 ± 0.1%) as compared to the healthy control group (1.2 ± 0.2%).…”

Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 99%

“…About 55.6% of HF patients have hemoglobin levels lower than 12 g·dL −1 . While ID has been widely implicated to cause anemia in HF, the anemia in a considerable number of patients is, however, refractory to treatment . Although different components have been proposed to contribute to HF‐associated anemia, the precise pathophysiology remains unclear.…”

Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 99%

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Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

et al. 2018

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The average lifespan of circulating erythrocytes usually exceeds hundred days. Prior to that, however, erythrocytes may be exposed to oxidative stress in the circulation which could cause injury and trigger their suicidal death or eryptosis. Oxidative stress activates Ca -permeable nonselective cation channels in the cell membrane, thus, stimulating Ca entry and subsequent cell membrane scrambling resulting in phosphatidylserine exposure and activation of Ca -sensitive K channels leading to K exit, hyperpolarization, Cl exit, and ultimately cell shrinkage due to loss of KCl and osmotically driven water. While the mechanistic link between oxidative stress and anemia remains ill-defined, several diseases such as diabetes, hepatic failure, malignancy, chronic kidney disease and inflammation have been identified to display both increased oxidative stress as well as eryptosis. Recent compelling evidence suggests that oxidative stress is an important perpetrator in accelerating erythrocyte loss in different systemic conditions and an underlying mechanism for anemia associated with these pathological states. In the present review, we discuss the role of oxidative stress in reducing erythrocyte survival and provide novel insights into the possible use of antioxidants as putative antieryptotic and antianemic agents in a variety of systemic diseases.

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Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 71%

Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 99%

Section: Clinical Conditions Stimulating Eryptosis By Generation Of Omentioning

confidence: 99%

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Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

et al. 2018

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“…The sensitivity to nocodazole may be particularly high in clinical conditions associated with enhanced eryptosis, such as dehydration [38], hyperphosphatemia [39] chronic kidney disease (CKD) [40][41][42][43], hemolytic-uremic syndrome [44], diabetes [45], hepatic failure [46], cardiac failure [47], malignancy [48], sepsis [49], fever [31,50], sickle-cell disease [31], betathalassemia [31], Hb-C and G6PD-deficiency [31], Wilsons disease [51] as well as advanced age [52]. Moreover, the effect of nocodazole may be compounded by other eryptosis stimulating xenobiotics [38,39,41,48,.…”

Section: Discussionmentioning

confidence: 99%

Nocodazole Induced Suicidal Death of Human Erythrocytes

Signoretto

Honisch

Briglia

et al. 2016

Cell Physiol Biochem

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Background: The microtubule assembly inhibitor nocodazole has been shown to trigger caspase-independent mitotic death and caspase dependent apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress and ceramide. The present study explored, whether and how nocodazole induces eryptosis. Methods: Flow cytometry was employed to determine phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence as well as ceramide surface abundance utilizing specific antibodies. Tubulin abundance was quantified by TubulinTracker™ Green reagent and visualized by confocal microscopy. Results: A 48 hours exposure of human erythrocytes to nocodazole (≥ 30 µg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying average forward scatter. Nocodazole significantly increased Fluo3-fluorescence, significantly increased DCF fluorescence and significantly increased ceramide surface abundance. The effect of nocodazole on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca²⁺ and was not modified in the presence of Caspase 3 inhibitor zVAD (1 µM). Nocodazole treatment reduced the content of total tubulin. Conclusions: Nocodazole triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca²⁺ entry, oxidative stress and ceramide.

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“…The eryptosis in malignancy is stimulated, at least in part, by a plasma component. The percentage of eryptotic erythrocytes was significantly higher following exposure of healthy Hepatic injury 12,13 Cardiac failure 14 Chronic kidney disease [15][16][17][18] Hemolytic uremic syndrome 1 erythrocytes to plasma from patients with lung cancer than to plasma from healthy individuals. 99 Mechanisms involved in the triggering of eryptosis by lung cancer include oxidative stress and ceramide abundance.…”

Section: Enhanced Eryptosis In Malignancymentioning

confidence: 99%

Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor‐associated anemia

Lang

Bissinger

Qadri

et al. 2017

Intl Journal of Cancer

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In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4. Eryptosis is inhibited by AMP-activated kinase, p21-activated kinase 2, cGMP-dependent protein-kinase, mitogen- and stress-activated kinase, and sorafenib- and sunitinib-sensitive tyrosine-kinases. Eryptosis is triggered by complement, hyperosmotic shock, energy-depletion, oxidative stress, multiple xenobiotics including diverse cytostatic drugs, diabetes, hepatic failure, iron-deficiency, chronic kidney disease, hemolytic-uremic-syndrome, fever, systemic lupus erythematosus, infections, sepsis, sickle cell anemia, thalassemia, glucose-6-phosphate-dehydrogenase deficiency, and Wilson´s disease. Compelling evidence points to a decisive role of eryptosis in anemia of malignancy. As shown for lung cancer, eryptosis inducing plasma components accumulate in cancer patients and trigger oxidative stress and ceramide. The tumor-induced eryptosis leads to anemia despite increased erythropoiesis. The stimulation of eryptosis in malignancy is compounded by cytostatic treatment, as a large number of cytostatic agents trigger eryptosis. Inhibiting eryptosis may be a useful strategy in reducing tumor-induced anemia and impaired microcirculation. Inhibitors of eryptosis may, however, be harmful, if they similarly interfere with death of tumor cells. Clearly, additional experimental effort is required to achieve killing of tumor cells with simultaneous avoidance of stimulated eryptosis.

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Enhanced suicidal erythrocyte death in acute cardiac failure

Abstract: AHF leads to anaemia despite increased reticulocyte number and at least partially due to enhanced eryptosis. Underlying mechanisms include oxidative stress imposed by a plasma borne component.

Cited by 26 publications

References 62 publications

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

Nocodazole Induced Suicidal Death of Human Erythrocytes

Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor‐associated anemia

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