Vitamin C Inhibits Aggravated Eryptosis by Hydrogen Peroxide in Glucose-6-Phosphated Dehydrogenase Deficiency

Shan, Feng; Yang, Rui; Ji, Tiemei; Jiao, Fengjun

doi:10.1159/000447848

Cited by 38 publications

(26 citation statements)

References 43 publications

(45 reference statements)

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“…The effect is at least partially due to increase C-reactive protein, which increases cytosolic Ca 2+ activity and ceramide formation in erythrocytes. As several inhibitors of eryptosis are available [2-4, 93, 94], eryptosis and subsequent development of anemia may be prevented.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

Abed

Thiel

Towhid

et al. 2017

Cell Physiol Biochem

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Background: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca²⁺-activity ([Ca²⁺]_i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies. Moreover, blood was drawn from patients with acute appendicitis (9♀,11♂) and healthy volunteers (10♀,10♂) for determination of CRP, blood count and phosphatidylserine. Results: A 48h CRP treatment significantly increased the percentage of annexin-V-binding cells (≥5µg/ml), [Ca²⁺]_i (≥5µg/ml), ceramide (20µg/ml) and caspase-activity (20µg/ml). Annexin-V-binding was significantly blunted by caspase inhibitor zVAD (10µM). The percentage of phosphatidylserine-exposing erythrocytes in freshly drawn blood was significantly higher in appendicitis patients (1.83±0.21%) than healthy volunteers (0.81±0.09%), and significantly higher following a 24h incubation of erythrocytes from healthy volunteers to patient plasma than to plasma from healthy volunteers. The percentage of phosphatidylserine-exposing erythrocytes correlated with CRP plasma concentration. Conclusion: C-reactive protein triggers eryptosis, an effect at least partially due to increase of [Ca²⁺]_i, increase of ceramide abundance and caspase activation.

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Section: Discussionmentioning

confidence: 99%

Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

Abed

Thiel

Towhid

et al. 2017

Cell Physiol Biochem

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“…Vitamin C and NAC have already been shown to inhibit eryptosis in vitro . Besides, vitamin C inhibits eryptosis in glucose‐6‐phosphate‐dehydrogenase deficiency .…”

Section: Pharmacological Inhibition Of Oxidative Stress In Erythrocytmentioning

confidence: 97%

“…To the extent that stimulated eryptosis may lead to anemia and thrombosis, it may be desirable to inhibit eryptosis. As a matter of fact, a wide variety of compounds such as blebbistatin, phlorhizin, vitamin C, resveratrol, reversine, hydroxytyrosol, volasertib, ASP3026 and teriflunomide have previously been shown to inhibit eryptosis in vitro . Some of these substances have previously been shown to counteract oxidative stress and may potentially be effective in vivo and could, therefore, be considered for the treatment of eryptosis‐induced anemia in different clinical conditions.…”

Section: Pharmacological Inhibition Of Oxidative Stress In Erythrocytmentioning

confidence: 99%

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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“…The adherence of eryptotic cells to vascular wall endothelial CXCL16/SR-PSO [61] and the binding of phosphatidylserine-exposing erythrocytes to blood platelets could further stimulate blood clotting and trigger thrombosis [62]. Eryptosis could also be induced by a wide range of xenobiotics [63-74], and enhanced eryptosis is observed in several clinical conditions, such as systemic lupus erythematosus [75], uremia under hemodialysis or peritoneal dialysis [76], pulmonary tumor [77], Parkinson’s disease [78], arteritis [79], hepatic failure [80, 81], tumor-induced anemia [82], vitamin D excess [83], advanced age [84], G6PD deficiency [85], sepsis [86], APC gene mutation and colon carcinoma [87]. Eryptosis can also be triggered by erythrocyte storage [88-90].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Suicidal Erythrocyte Death by Indirubin-3’-Monoxime

Liu

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Qing Dai is a prized traditional Chinese medicine whose major component, indirubin, and its derivative, indirubin-3’-monoxime (IDM), have inhibitory effects on the growth of many human tumor cells and pronounced anti-leukemic activities. However, the effects of IDM on mature human erythrocytes are unclear. This study aimed to evaluate the potential impact of IDM on erythrocytes and the mechanisms underlying that impact. Methods: Utilizing flow cytometry and confocal laser scanning microscopy, phosphatidylserine exposure at the cell surface was estimated by annexin V-fluorescein isothiocyanate (FITC). The relative cell size, expressed in arbitrary units, was evaluated by forward scatter in a flow cytometer. Fluo-3 fluorescence was used to bewrite changes in cytosolic Ca²⁺ activity, reactive oxygen species (ROS) formation was assessed by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence, and ceramide abundance was evaluated by FITC-conjugated specific antibodies. Results: The 24-h exposure of human erythrocytes to IDM (12 µM) significantly decreased the percentage of annexin V-binding erythrocytes and the intracellular calcium concentration ([Ca²⁺]_i). IDM (3-12 µM) did not significantly modify the ceramide level or DCFH-DA fluorescence. Energy depletion (removal of glucose for 24 hours) significantly increased annexin V binding and Fluo-3 fluorescence and diminished forward scatter, and these effects were significantly mitigated by IDM (12 µM). Moreover, the Ca²⁺ ionophore ionomycin (1 µM, 60 min) and oxidative stress (30 min exposure to 0.05 mM tert-butyl hydroperoxide, t-BHP) similarly triggered eryptosis, which was also significantly suppressed by IDM. Conclusions: IDM is a novel inhibitor of suicidal erythrocyte death following ionomycin treatment, t-BHP treatment and energy depletion. Thus, IDM may counteract anemia and impairment of microcirculation, at least in part, by inhibition of Ca²⁺ entry into erythrocytes.

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Vitamin C Inhibits Aggravated Eryptosis by Hydrogen Peroxide in Glucose-6-Phosphated Dehydrogenase Deficiency

Cited by 38 publications

References 43 publications

Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

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

Inhibition of Suicidal Erythrocyte Death by Indirubin-3’-Monoxime

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