CD95 is not functional in human erythrocytes

Sagan, Daniel; Jermnim, Nangnoi; Tangvarasittichai, Orathai

doi:10.1111/j.1751-553x.2010.01245.x

Cited by 8 publications

(7 citation statements)

References 17 publications

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“…Normally these conditions trigger apoptosis in nucleated cells [102]. The next studies confirmed that caspase-8 and caspase-3 cannot be activated by CD95-stimulating antibody [103], etoposide or mitomycin c [100], well known inducers of apoptosis. More recent studies revealed that induction of the Fas-mediated cell death cascade may be a result of reactive oxygen species (ROS) and cholesterol accumulation in the erythrocytes of animals exposed to arsenic derivatives (e.g., sodium arsenite) [104,105].…”

Section: Mature Erythrocytes and Extrinsic Apoptotic Pathwaysupporting

confidence: 58%

Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia

Raducka-Jaszul

Bogusławska

Jędruchniewicz

et al. 2020

IJMS

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Apoptosis is a process of programmed cell death which has an important role in tissue homeostasis and in the control of organism development. Here, we focus on information concerning the role of the extrinsic apoptotic pathway in the control of human erythropoiesis. We discuss the role of tumor necrosis factor α (TNFα), tumor necrosis factor ligand superfamily member 6 (FasL), tumor necrosis factor-related apoptosis-inducing (TRAIL) and caspases in normal erythroid maturation. We also attempt to initiate a discussion on the observations that mature erythrocytes contain most components of the receptor-dependent apoptotic pathway. Finally, we point to the role of the extrinsic apoptotic pathway in ineffective erythropoiesis of different types of β-thalassemia.

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Section: Mature Erythrocytes and Extrinsic Apoptotic Pathwaysupporting

confidence: 58%

Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia

Raducka-Jaszul

Bogusławska

Jędruchniewicz

et al. 2020

IJMS

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“…These include dependence on RIP1 phosphorylation, MLKL, and extrinsic ligands of the TNF superfamily (e.g., FasL); antagonism by caspase-8; and necrosome assembly. Moreover, whereas Fas and FasL differ in their cellular localizations during oxidative stress and in senescent RBCs (18), they were reported to be nonfunctional in mature RBCs (37, 39). Nonetheless, we show that Fas and FasL drive programmed necrosis in mature RBCs, promoting RIP1 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

LaRocca

Stivison

Hod

et al. 2014

mBio

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A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis.

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“…Erythrocyte cell membrane scrambling could be further triggered by caspases (11,43), which are activated by oxidative stress but are not required for the scrambling effect of Ca 2ϩ (5,62). Similarly, CD95 appears not to be important for suicidal erythrocyte death (55).…”

mentioning

confidence: 99%

Inhibition of suicidal erythrocyte death by blebbistatin

Lang

Qadri

Zelenak

et al. 2011

American Journal of Physiology-Cell Physiology

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Blebbistatin, a myosin II inhibitor, interferes with myosin-actin interaction and microtubule assembly. By influencing cytoskeletal dynamics blebbistatin counteracts apoptosis of several types of nucleated cells. Even though lacking nuclei and mitochondria, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include energy depletion and osmotic shock, which enhance cytosolic Ca(2+) activity with subsequent Ca(2+)-sensitive cell shrinkage and cell membrane scrambling. The present study explored the effect of blebbistatin on eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in fluorescence-activated cell sorting analysis and cytosolic Ca(2+) concentration from Fluo3 fluorescence. Exposure to blebbistatin on its own (1-50 μM) did not significantly modify cytosolic Ca(2+) concentration, forward scatter, or annexin V binding. Glucose depletion (48 h) was followed by a significant increase of Fluo3 fluorescence and annexin V binding, effects significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 10 μM). Osmotic shock (addition of 550 mM sucrose) again significantly increased Fluo3 fluorescence and annexin binding, effects again significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 25 μM). The present observations disclose a novel effect of blebbistatin, i.e., an influence on Ca(2+) entry and suicidal erythrocyte death following energy depletion and osmotic shock.

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CD95 is not functional in human erythrocytes

Abstract: Based on some key features for an activated CD95 system, this death receptor has been considered to induce PS exposure. However, we give evidence, that CD95 is not functional in red blood cells and that activation of this death receptor does not lead to the exposure of phosphatidylserine.

Cited by 8 publications

References 17 publications

Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia

Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

Inhibition of suicidal erythrocyte death by blebbistatin

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