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2 results on '"Catherine Bouchenot"'

1. Dairy By-Products and Lactoferrin Exert Antioxidant and Antigenotoxic Activity on Intestinal and Hepatic Cells

Author

Inés Abad, Julien Vignard, Catherine Bouchenot, Dimitra Graikini, Laura Grasa, María Dolores Pérez, Gladys Mirey, and Lourdes Sánchez

Subjects
buttermilk, whey, lactoferrin, oxidative stress, DNA damage, bioavailability, Chemical technology, TP1-1185
Abstract

The dairy industry generates a large volume of by-products containing bioactive compounds that may have added value. The aim of this study was to evaluate the antioxidant and antigenotoxic effects of milk-derived products, such as whey, buttermilk, and lactoferrin, in two human cell lines: Caco-2 as an intestinal barrier model and HepG2 as a hepatic cell line. First, the protective effect of dairy samples against the oxidative stress caused by menadione was analyzed. All these dairy fractions significantly reversed the oxidative stress, with the non-washed buttermilk fraction presenting the greatest antioxidant effect for Caco-2 cells and lactoferrin as the best antioxidant for HepG2 cells. At concentrations that did not impact cell viability, we found that the dairy sample with the highest antigenotoxic power against menadione, in both cell lines, was lactoferrin at the lowest concentration. Additionally, dairy by-products maintained their activity in a coculture of Caco-2 and HepG2, mimicking the intestinal-liver axis. This result suggests that the compounds responsible for the antioxidant activity could cross the Caco-2 barrier and reach HepG2 cells on the basal side, exerting their function on them. In conclusion, our results show that dairy by-products have antioxidant and antigenotoxic activities, which would allow revaluing their use in food specialties.

Published
2023
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2. Chronic exposure to Cytolethal Distending Toxin (CDT) promotes a cGAS-dependent type I interferon response

Author

Claire Naylies, Gladys Mirey, Patrick Rouimi, Benoît J. Pons, Maxime Deslande, Saleha Hashim, Julien Vignard, Catherine Bouchenot, Yannick Lippi, Frédéric Taieb, Aurélie Pettes-Duler, Génotoxicité & Signalisation (ToxAlim-GS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Contaminants & Stress Cellulaire (ToxAlim-COMICS), This work was supported by the ANR Grant No ANR-10-CESA-011 to G. Mirey, the Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE) and the Toxalim internal program to J. Vignard. B.J. Pons was supported by a Ph.D. fellowship granted by the COLiveTox IDEX Toulouse University., ANR-10-CESA-0011,GENOTOXTRACK,Biomarqueurs de génotoxicité ex vivo et in vivo.(2010), Vignard, Julien, CONTAMINANTS, ECOSYSTEMES, SANTE - Biomarqueurs de génotoxicité ex vivo et in vivo. - - GENOTOXTRACK2010 - ANR-10-CESA-0011 - CES - VALID, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim)

Subjects
0301 basic medicine, Cell division, Cytolethal distending toxin, [SDV]Life Sciences [q-bio], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], DNA damage response, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mice, 0302 clinical medicine, Interferon, DNA Breaks, Double-Stranded, Nucleotidyltransferases, 3. Good health, Cell biology, Up-Regulation, Interferon Type I, cGAS-STING axis, Molecular Medicine, medicine.drug, DNA damage, Bacterial Toxins, Bacterial genotoxin, Mitosis, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Immune system, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Animals, Humans, Fragmentation (cell biology), [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Interferon-stimulated genes, Molecular Biology, Pharmacology, Epithelial Cells, Cell Biology, Cell Cycle Checkpoints, Fibroblasts, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Micronucleus, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carcinogenesis, 030217 neurology & neurosurgery, HeLa Cells
Abstract

The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin produced by pathogenic bacteria causing major foodborne diseases worldwide. CDT activates the DNA Damage Response and modulates the host immune response, but the precise relationship between these outcomes has not been addressed so far. Here, we show that chronic exposure to CDT in HeLa cells or mouse embryonic fibroblasts promotes a strong type I interferon (IFN) response that depends on the cytoplasmic DNA sensor cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) through the recognition of micronuclei. Indeed, despite active cell cycle checkpoints and in contrast to other DNA damaging agents, cells exposed to CDT reach mitosis where they accumulate massive DNA damage, resulting in chromosome fragmentation and micronucleus formation in daughter cells. These mitotic phenotypes are observed with CDT from various origins and in cancer or normal cell lines. Finally, we show that CDT exposure in immortalized normal colonic epithelial cells is associated to cGAS protein loss and low type I IFN response, implying that CDT immunomodulatory function may vary depending on tissue and cell type. Thus, our results establish a direct link between CDT-induced DNA damage, genetic instability and the cellular immune response that may be relevant in the context of natural infection associated to chronic inflammation or carcinogenesis.

Published
2021

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