Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas‐mediated signaling DOI
Ignazio Restivo, Ilenia Concetta Giardina, Rosario Barone

et al.

BioFactors, Journal Year: 2024, Volume and Issue: 50(5), P. 997 - 1008

Published: March 23, 2024

Abstract A physiological mechanism of programmed cell death called eryptosis occurs in aged or damaged red blood cells (RBCs). Dysregulated contributes to abnormal microcirculation and prothrombotic risk. Cigarette smoke extract (CSE) induces a p38 MAPK‐initiated, Fas‐mediated eryptosis, activating the death‐inducing signaling complex (DISC). Indicaxanthin (Ind) from cactus pear fruits, is bioavailable dietary phytochemical humans it able incorporate into RBCs enhancing their defense against numerous stimuli. This vitro work shows that Ind, at concentrations mimic plasma after fruit meal, protects erythrocytes CSE‐induced eryptosis. CSE commercial cigarettes was prepared aqueous solution using an impinger air sampler nicotine content determined. were treated with for 3 h absence presence increasing Ind (from 1 5 μM). Cytofluorimetric measurements indicated reduced phosphatidylserine externalization ceramide formation concentration‐dependent manner. Confocal microscopy visualization coimmunoprecipitation experiments revealed prevented both CSE‐triggered Fas aggregation FasL/FADD/caspase 8 recruitment membrane, indicating inhibition DISC assembly. inhibited phosphorylation MAPK, caspase‐8/caspase‐3 cleavage, caspase‐3 activity induced by CSE. Finally, ATP depletion restored aminophospholipid translocase impaired treatment. In conclusion, comparable nutritionally relevant concentrations, can prevent RBC CSE, which suggests intake fruits may limit deleterious effects cigarette smoking.

Language: Английский

Stimulation of Hemolysis and Eryptosis by α-Mangostin through Rac1 GTPase and Oxidative Injury in Human Red Blood Cells DOI Creative Commons

Sumiah A. Alghareeb,

Jawaher Alsughayyir, Mohammad A. Alfhili

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(18), P. 6495 - 6495

Published: Sept. 7, 2023

Chemotherapy-related anemia is prevalent in up to 75% of patients, which may arise due hemolysis and eryptosis. Alpha-mangostin (α-MG) a polyphenolic xanthonoid found the mangosteen tree (Garcinia mangostana) whose antitumor medicinal properties are well-established. Nevertheless, potential toxic effects α-MG on red blood cells (RBCs) have, as yet, not been well studied.RBCs were exposed 1-40 μM for 24 h at 37 °C. Hemolysis related markers measured using colorimetric assays, eryptotic identified through Annexin-V-FITC, Ca2+ was detected with Fluo4/AM, oxidative stress assessed H2DCFDA flow cytometry. The toxicity also examined presence specific signal transduction inhibitors whole blood.α-MG 10-40 caused dose-dependent concurrent significant elevation K+, Mg2+, LDH leakage, but 2.5 it significantly increased osmotic resistance cells. A increase noted Annexin-V-binding cells, along intracellular Ca2+, stress, cell shrinkage. Moreover, acetylcholinesterase activity inhibited by α-MG, hemolytic ameliorated BAPTA-AM, vitamin C, NSC23766, isosmotic sucrose urea. In blood, depleted hemoglobin stores selectively platelets monocytes.α-MG possesses activities mediated signaling, Rac1 GTPase activity, injury. Also, leads accelerated cellular aging specifically targets platelet monocyte populations milieu.

Language: Английский

Citations

7
Eriocitrin Disrupts Erythrocyte Membrane Asymmetry through Oxidative Stress and Calcium Signaling and the Activation of Casein Kinase 1α and Rac1 GTPase DOI Creative Commons

Sumiah A. Alghareeb,

Jawaher Alsughayyir, Mohammad A. Alfhili

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1681 - 1681

Published: Dec. 2, 2023

Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes thus contribute to chemotherapy-related anemia, which is extremely prevalent cancer patients. Eriocitrin (ERN), a flavanone glycoside citrus fruits, has shown great promise as an anticancer agent, but potential toxicity ERN human remains unstudied.Erythrocytes were exposed concentrations (10-100 μM) for 24 h at 37 °C, hemolysis associated markers quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis detect phosphatidylserine (PS) exposure annexin-V-FITC, intracellular Ca2+ Fluo4/AM, oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H2DCFDA). also tested against specific signaling inhibitors anti-hemolytic agents.ERN caused significant, concentration-dependent 20-100 μM. significantly increased percentage eryptotic cells characterized elevation stress. Furthermore, hemolytic activity ameliorated presence D4476, NSC23766, isosmotic urea sucrose, polyethylene glycol 8000 (PEG). In whole blood, elevated MCV ESR, no appreciable effects on other peripheral blood cells.ERN promotes erythrocyte death through PS externalization, accumulation, membrane blebbing, loss cellular volume, These toxic effects, mediated casein kinase 1α Rac1 GTPase, can be urea, PEG. Altogether, these novel findings are relevant further development therapeutic.

Language: Английский

Citations

6
Protective effects of olive oil antioxidant phenols on mercury-induced phosphatidylserine externalization in erythrocyte membrane: insights into scramblase and flippase activity. DOI Creative Commons
Pasquale Perrone, Rosaria Notariale, Gennaro Lettieri

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

2
The Impact of Calcium Overload on Cellular Processes: Exploring Calcicoptosis and Its Therapeutic Potential in Cancer DOI Open Access
Adrianna Gielecińska, Mateusz Kciuk, Renata Kontek

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13727 - 13727

Published: Dec. 23, 2024

The key role of calcium in various physiological and pathological processes includes its involvement forms regulated cell death (RCD). concept ‘calcicoptosis’ has been introduced as a calcium-induced phenomenon associated with oxidative stress cellular damage. However, definition remains controversial within the research community, some considering it general form overload stress, while others view tumor-specific death. This review examines context established RCD mechanisms such apoptosis, necroptosis, ferroptosis, others. It further analyzes intricate relationship between dysregulation emphasizing that often triggers death, may not represent an entirely new type but rather extension known pathways. purpose this paper is to discuss implications perspective for cancer therapy focusing on calcium-based nanoparticles. By investigating connections dynamics pathways, contributes advancement our understanding calcicoptosis possible therapeutic uses.

Language: Английский

Citations

2
Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas‐mediated signaling DOI
Ignazio Restivo, Ilenia Concetta Giardina, Rosario Barone

et al.

BioFactors, Journal Year: 2024, Volume and Issue: 50(5), P. 997 - 1008

Published: March 23, 2024

Abstract A physiological mechanism of programmed cell death called eryptosis occurs in aged or damaged red blood cells (RBCs). Dysregulated contributes to abnormal microcirculation and prothrombotic risk. Cigarette smoke extract (CSE) induces a p38 MAPK‐initiated, Fas‐mediated eryptosis, activating the death‐inducing signaling complex (DISC). Indicaxanthin (Ind) from cactus pear fruits, is bioavailable dietary phytochemical humans it able incorporate into RBCs enhancing their defense against numerous stimuli. This vitro work shows that Ind, at concentrations mimic plasma after fruit meal, protects erythrocytes CSE‐induced eryptosis. CSE commercial cigarettes was prepared aqueous solution using an impinger air sampler nicotine content determined. were treated with for 3 h absence presence increasing Ind (from 1 5 μM). Cytofluorimetric measurements indicated reduced phosphatidylserine externalization ceramide formation concentration‐dependent manner. Confocal microscopy visualization coimmunoprecipitation experiments revealed prevented both CSE‐triggered Fas aggregation FasL/FADD/caspase 8 recruitment membrane, indicating inhibition DISC assembly. inhibited phosphorylation MAPK, caspase‐8/caspase‐3 cleavage, caspase‐3 activity induced by CSE. Finally, ATP depletion restored aminophospholipid translocase impaired treatment. In conclusion, comparable nutritionally relevant concentrations, can prevent RBC CSE, which suggests intake fruits may limit deleterious effects cigarette smoking.

Language: Английский

Citations

1