Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling.

betalains cell death cigarette smoke eryptosis erythrocytes indicaxanthin

Journal

BioFactors (Oxford, England)
ISSN: 1872-8081
Titre abrégé: Biofactors
Pays: Netherlands
ID NLM: 8807441

Informations de publication

Date de publication:
23 Mar 2024
Historique:
received: 22 11 2023
accepted: 19 02 2024
medline: 23 3 2024
pubmed: 23 3 2024
entrez: 23 3 2024
Statut: aheadofprint

Résumé

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

Identifiants

pubmed: 38520710
doi: 10.1002/biof.2051
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Università degli Studi di Palermo

Informations de copyright

© 2024 International Union of Biochemistry and Molecular Biology.

Références

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Auteurs

Ignazio Restivo (I)

Department of Biological, Chemical and Pharmaceutical Science and Technologies, Università degli Studi di Palermo, Palermo, Italy.

Ilenia Concetta Giardina (IC)

Department of Biological, Chemical and Pharmaceutical Science and Technologies, Università degli Studi di Palermo, Palermo, Italy.

Rosario Barone (R)

Department of Biomedicine, Neuroscience and Advanced Diagnostics, Section of Human Anatomy, Università di Palermo, Palermo, Italy.

Antonio Cilla (A)

Nutrition and Food Science Area, Faculty of Pharmacy and Food Sciences, University of Valencia, Burjassot, Valencia, Spain.

Stefano Burgio (S)

Department of Biomedicine, Neuroscience and Advanced Diagnostics, Section of Human Anatomy, Università di Palermo, Palermo, Italy.

Mario Allegra (M)

Department of Biological, Chemical and Pharmaceutical Science and Technologies, Università degli Studi di Palermo, Palermo, Italy.

Luisa Tesoriere (L)

Department of Biological, Chemical and Pharmaceutical Science and Technologies, Università degli Studi di Palermo, Palermo, Italy.

Alessandro Attanzio (A)

Department of Biological, Chemical and Pharmaceutical Science and Technologies, Università degli Studi di Palermo, Palermo, Italy.

Classifications MeSH