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25 results on '"Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB)"'

1. Spatial localization and binding of the probiotic Lactobacillus farciminis to the rat intestinal mucosa: influence of chronic stress

Author: Muriel Mercier-Bonin, Vassilia Theodorou, Christel Salvador-Cartier, Afifa Ait-Belgnaoui, Pascal Loubière, Catherine Robbe-Masselot, Bélinda Ringot, Isabelle Fourquaux, Myriam Mercade-Loubière, Stéphanie Da Silva, Arthur Raymond, Renaud Léonard, Da Silva, Stéphanie, Robbe Masselot, Catherine, Théodorou, Vassilia, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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, Université Lille Nord de France (COMUE), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université des Sciences et Technologies (Lille 1) (USTL), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lallemand S.A.S., Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), INRA (CEPIA Division), CNRS (INSIS Institute), Lallemand SA, Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Lille, Sciences et Technologies, Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CNRS, Université de Lille, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés [LISBP], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], ToxAlim [ToxAlim], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], and Centre de Microscopie Électronique Appliquée à la Biologie [CMEAB]
Subjects: Male, [SDV]Life Sciences [q-bio], lcsh:Medicine, Mucin 2, localization, law.invention, Probiotic, Intestinal mucosa, law, Lactobacillus, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Chronic stress, rat, Intestinal Mucosa, lcsh:Science, muqueuse intestinale, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, probiotique, medicine.anatomical_structure, probiotic, Research Article, Protein Binding, Colon, Population, lactobacillus farciminis, Ileum, Gastroenterology and Hepatology, Microbiology, 03 medical and health sciences, mucus, IBS, medicine, Gastroenterologi, Animals, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Rats, Wistar, education, 030304 developmental biology, Mucin-2, 030306 microbiology, animal model, lcsh:R, biology.organism_classification, Epithelium, Rats, stress chronique, lcsh:Q, Stress, Psychological
Abstract: International audience; The present study aimed at detecting the exogenously applied probiotic Lactobacillus farciminis in rats, after exposure to IBS-like chronic stress, based on 4-day Water Avoidance Stress (WAS). The presence of L. farciminis in both ileal and colonic mucosal tissues was demonstrated by FISH and qPCR, with ileum as the preferential niche, as for the SFB population. A different spatial distribution of the probiotic was observed: in the ileum, bacteria were organized in micro-colonies more or less close to the epithelium whereas, in the colon, they were mainly visualized far away from the epithelium. When rats were submitted to WAS, the L. farciminis population substantially decreased in both intestinal regions, due to a stress-induced increase in colonic motility and defecation, rather than a modification of bacterial binding to the intestinal mucin Muc2.
Published: 2015

2. Cold helium plasma jet does not stimulate collagen remodeling in a 3D human dermal substitute

Author: Laure Gibot, Aurélie Marches, Isabelle Fourquaux, Patricia Vicendo, Sara Gouarderes, Michel Simon, Nofel Merbahi, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), IDeAS - Interfaces Dynamiques et Assemblages Stimulables (IDeAS), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Plasmas Réactifs Hors Equilibre (LAPLACE-PRHE), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), GDR HAPPYBIO, ANR-17-CE19-0013,WHEEL,Comment l'électricité stimule la cicatrisation : vers une thérapie plus performante des plaies(2017), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Merbahi, Nofel, Comment l'électricité stimule la cicatrisation : vers une thérapie plus performante des plaies - - WHEEL2017 - ANR-17-CE19-0013 - AAPG2017 - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul)
Subjects: matrix metalloproteinase, Plasma Gases, [SPI] Engineering Sciences [physics], Biophysics, Wound healing, Matrix metalloproteinase, cold atmospheric plasma, metalloproteinases MMPs, Extracellular matrix, 03 medical and health sciences, Hydroxyproline, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], 0302 clinical medicine, In vivo, Electrochemistry, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Secretion, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Viability assay, Physical and Theoretical Chemistry, wound healing ABBREVIATIONS: CAP, reactive oxygen and nitrogen species, 030304 developmental biology, Skin, [SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, MESH: Plasma Gases, ECM, Plasma-activated medium (PAM), MESH: Humans, MMP, Chemistry, plasma-activated medium, Cold atmospheric plasma (CAP), General Medicine, In vitro, Cell biology, RONS, Oxidative stress, 030220 oncology & carcinogenesis, PAM, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; Cold Atmospheric Plasma (CAP) is an emerging physical approach displaying encouraging antitumor and wound healing effects both in vitro and in vivo. In this study, we assessed the potential of direct CAP to remodel skin collagens using an original tissue-engineered human dermal substitute model rich in endogenous extracellular matrix (ECM) covered with 600 µl of culture medium and treated with CAP for 30 and 120 seconds. Our results indicated that Reactive Oxygen and Nitrogen Species such as H2O2, NO3- and NO2- were produced in the medium during treatment. It appeared that in the CAP-treated dermal substitutes 1) cell viability was not altered, 2) pro-collagen I secretion was not modified over 48 h of culture after treatment, 3) global activity of matrix metalloproteinases was not modulated over 48 h after treatment, and 4) no change in hydroxyproline content was observed over 5 days after treatment. In order to confirm the efficiency of our device, we showed that the plasma-activated culture medium induced cell apoptosis and growth delay using a 3D human tumor spheroid model. In conclusion, no effect of direct CAP treatment was monitored on ECM production and degradation, indicating that CAP does not stimulate collagen remodeling at the tissue scale.
Published: 2022

3. Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties

Author: Mina Raileanu, Laure Gibot, Mihaela Bacalum, Barbara Lonetti, Dominique Goudounèche, Charles-Louis Serpentini, University of Bucharest (UniBuc), Horia Hulubei National Institute for Physics and Nuclear Engineering, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), IDeAS - Interfaces Dynamiques et Assemblages Stimulables (IDeAS), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Gibot, Laure
Subjects: [CHIM.POLY] Chemical Sciences/Polymers, Antimicrobial peptides, Peptide, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, [SDV.SP.PG] Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Micelle, Analytical Chemistry, Inorganic Chemistry, poly(ethylene oxide)-poly(acrylic acid) (PEO-PAA), 03 medical and health sciences, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, micelle, Spectroscopy, polymers, 030304 developmental biology, Acrylic acid, chemistry.chemical_classification, 0303 health sciences, Organic Chemistry, Cationic polymerization, self-assembly, 021001 nanoscience & nanotechnology, Antimicrobial, Combinatorial chemistry, polyionic complex (PIC), [CHIM.POLY]Chemical Sciences/Polymers, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, chemistry, spheroid, Drug delivery, Self-assembly, 0210 nano-technology
Abstract: International audience; Antimicrobial peptides, a large class of molecules synthetized by various organisms as an innate defense against pathogens are more and more used for their anticancer properties as well. In order to overcome some of their limitations and to enhance their therapeutic efficiency, the use of delivery systems was taken into consideration. In this study we describe an original delivery system for antimicrobial peptides based on its physico-chemical properties, namely the selfassembled polyion complexes (PIC) based on electrostatic interactions of cationic antimicrobial peptide P6 with negatively charged double hydrophilic block copolymers, the poly(ethylene oxide)-poly(acrylic acid) (PEO-PAA) in our study. The drug delivery system was tested on 3D human tumor HCT-116 spheroids. The spheroid evolution and cell viability were monitored at 24 and 48 h after the treatment was applied. Our study demonstrates for the first time the feasibility of forming a polyion complex PIC with an antimicrobial peptide and that this self-assembled organisation provides added value in terms of anti-tumour therapeutic efficacy compared to the free form of the antimicrobial peptide.
Published: 2022

4. Uptake, fate, and gut toxicity of perfluorooctanoic acid (PFOA) in vitro

Author: Muriel Mercier-Bonin, Hervé Robert, N. Cabaton, Jean-Nicolas Audinot, C. Stoffels, Mathilde Leveque, Isabelle Fourquaux, E. Person, Vassilia Theodorou, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), 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), Luxembourg Institute of Science and Technology (LIST), Métabolisme et Xénobiotiques (ToxAlim-MeX), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
Subjects: 0303 health sciences, [SDV]Life Sciences [q-bio], General Medicine, Toxicology, In vitro, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Biochemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Perfluorooctanoic acid, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

5. Structure and biological activities of a hexosamine-rich cell wall polysaccharide isolated from the probiotic Lactobacillus farciminis

Author: Irina Sadovskaya, Bruno Payré, Elisabeth Elass-Rochard, Thierry Grard, Vassilia Theodorou, Yann Guérardel, Mathilde Leveque, Muriel Mercier-Bonin, Emmanuel Maes, Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Institut Charles Viollette (ICV) - ULR 7394, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Equipe APA, Université du Littoral Côte d'Opale (ULCO), Centre d'Etudes sur les Nouveaux Espaces Littéraires (CENEL), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC), CMEAB, Faculté de Médecine Rangueil, Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lille-Université du Littoral Côte d'Opale (ULCO)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut national des sciences de l'Univers (INSU - CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université du Littoral Côte d'Opale-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Biochimie des Produits Aquatiques (BPA), Université du Littoral Côte d'Opale (ULCO)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Polysaccharide, Probiotic, Biochemistry, Immunomodulation, 03 medical and health sciences, Cell Wall, medicine, Humans, Cell wall polysaccharide, Receptor, Molecular Biology, Intestinal barrier, ComputingMilieux_MISCELLANEOUS, Lactobacillus farciminis, Cytokines, HEK293 Cells, Hexosamines, Lactobacillus, Polysaccharides, Bacterial, Probiotics, Signal Transduction, Toll-Like Receptors, Structure, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, 030302 biochemistry & molecular biology, HEK 293 cells, Cell Biology, Transfection, Methylation, Epithelium, In vitro, TLR2, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], medicine.anatomical_structure
Abstract: International audience; Lactobacillus farciminis CIP 103136 is a bacterial strain with recognized probiotic properties. However, the mechanisms underlying such properties have only been partially elucidated. In this study, we isolated and purified a cell-wall associated polysaccharide (CWPS), and evaluated its biological role in vitro. The structure of CWPS and responses from stimulation of (i) human macrophage-like THP-1 cells, (ii) human embryonal kidney (HEK293) cells stably transfected with Toll-like receptors (TLR2 or TLR4) and (iii) human colonocyte-like T84 intestinal epithelial cells, upon exposure to CWPS were studied. The structure of the purified CWPS from L. farciminis CIP 103136 was analyzed by nuclear magnetic resonance (NMR), MALDI-TOF-TOF MS, and methylation analyses in its native form and following Smith degradation. It was shown to be a novel branched polysaccharide, composed of linear backbone of trisaccharide repeating units of: [6GlcpNAc14ManpNAc14GlcpNAc1] highly substituted with single residues of Glcp, Galp and GlcpNAc. Subsequently, the lack of pro- or anti-inflammatory properties of CWPS was established on macrophage-like THP-1 cells. In addition, CWPS failed to modulate cell signaling pathways dependent of TLR2 and TLR4 in transfected HEK-cells. Finally, in T84 cells, CWPS neither influenced intestinal barrier integrity under basal conditions nor prevented TNF-/IFN- cytokine-mediated epithelium impairment.
Published: 2019

6. Pectin Demethylesterification Generates Platforms that Anchor Peroxidases to Remodel Plant Cell Wall Domains

Author: Philippe Ranocha, Vincent Burlat, Alain Jauneau, Isabelle Fourquaux, Aurélie Le Ru, Christophe Dunand, Yves Martinez, Edith Francoz, Laboratoire de Recherche en Sciences Végétales (LRSV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Dynamique et Evolution des Parois cellulaires végétales, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Fédération de Recherche Agrobiosciences, Interactions et Biodiversité (FR AIB), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Scaffold, food.ingredient, Pectin, Arabidopsis thaliana, plant cell wall domain, Arabidopsis, seed mucilage secretory cells, homogalacturonan methylesterification, General Biochemistry, Genetics and Molecular Biology, Domain (software engineering), Cell wall, 03 medical and health sciences, 0302 clinical medicine, food, Cell Wall, Gene Expression Regulation, Plant, class III peroxidase, FRET-FLIM immunofluorescence, Molecular Biology, 030304 developmental biology, 0303 health sciences, Physiological function, Molecular interactions, protein-polysaccharide interaction, biology, Arabidopsis Proteins, Plant Extracts, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, biology.organism_classification, PRX36, Cell biology, Peroxidases, PMEI6, Mutation, Seeds, Pectins, 030217 neurology & neurosurgery, pectin methylesterase inhibitor, Developmental Biology
Abstract: International audience; Plant cell walls are made of polysaccharidic-proteinaceous complex matrices. Molecular interactions governing their organization remain understudied. We take advantage of the highly dynamic cell walls of Arabidopsis seed mucilage secretory cells to propose a hierarchical multi-molecular interaction model within a cell wall domain. We show that the PECTINMETHYLESTERASE INHIBITOR6 activity creates a partially demethylesterified pectin pattern acting as a platform allowing positioning of PEROXIDASE36 in a remote primary cell wall domain during early development. This allows triggering the loosening of this domain during later development, in turn leading to proper physiological function upon mature seed imbibition and germination. We anticipate that this pioneer example of molecular scaffold within a cell wall domain is more widespread through other combinations of the individual molecular players all belonging to large multigenic families. These results highlight the role of cell wall polysaccharide-protein interactions in the organization of cell wall domains.
Published: 2019

7. Direct and indirect effects of bioactive tannin-rich tropical and temperate legumes against nematode infections

Author: S. Brunet, F. Manolaraki, I. Fourquaux, C. Martinez-Ortiz-De-Montellano, Juan Felipe de Jesús Torres-Acosta, Carlos A. Sandoval-Castro, Nadia Florencia Ojeda-Robertos, H. Hoste, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-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-Université Fédérale Toulouse Midi-Pyrénées, Universidad Autónoma de Yucatán, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Nematoda, Gastrointestinal Diseases, 040301 veterinary sciences, Drug Resistance, Sheep Diseases, 030308 mycology & parasitology, 0403 veterinary science, Lysiloma latisiliquum, Feces, 03 medical and health sciences, medicine, Animals, Proanthocyanidins, Anthelmintic, Nematode Infections, tannin rich fodder, polyphenols, Anthelmintics, gastrointestinal nematodes, 0303 health sciences, Sheep, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Resistance (ecology), biology, Ecology, business.industry, Fabaceae, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, Animal Feed, GINS, Nematode, Onobrychis, ruminants, Dietary Supplements, Female, Parasitology, Livestock, nutraceutical, business, medicine.drug
Abstract: International audience; Parasitic infections with gastrointestinal nematodes (GINs) represent a major pathological threat associated with the outdoor production of various livestock species. Up to now, the control of these parasitic diseases essentially relied on the use of commercial anthelmintic drugs. However, resistance to anthelmintics is nowadays widespread in worm populations. Recent results indicate that bioactive tanniniferous plants represent a valuable option as an alternative to commercial drugs for the control of GINs. The pertinent use of tannincontaining fodders as nutraceuticals supposes a clear understanding of the mode of action against the worms. The objectives of this paper are: (1) to discuss the nature and quantity of the active molecules involved in the anthelmintic activity; and (2) to review and analyze the changes provoked to the various parasitic stages. The possible involvement of some main polyphenols to explain the bioactivity of some tannin-rich plants will be discussed as well as the possible effects on the various nematode stages, relying on data obtained either with the temperate forage, sainfoin (Onobrychis viciifoliae) or with the tropical legume tree (Lysiloma latisiliquum). The information on the mode of action will be related to the potential consequences for better field applications under entirely different environmental and ecological conditions of productions.
Published: 2012

8. Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

Author: Christophe Heymes, Michael D. Schneider, Céline Galés, Benjamin Honton, Denis Calise, Alexandre Dubrac, Christelle Coatrieux, Alice Davy, Etienne Dague, Christelle Cardin, Jean-Michel Senard, Marie-Hélène Seguelas, Fabien Despas, Bruno Payré, Marie-Bernadette Delisle, Céline Guilbeau-Frugier, Dina N. Arvanitis, Gael Genet, Caroline Dubroca, Pauline Marck, Marie-Françoise Altié, Atul Pathak, Cécile Nieto, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute, Imperial College London-British Heart Foundation, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de biologie du développement (CBD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Simon, Marie Francoise, Service d'histopathologie, CHU Toulouse [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), and Laboratoire de pharmacologie médicale et clinique
Subjects: Male, Physiology, MESH: Myocytes, Cardiac, Cell Communication, Matrix (biology), MESH: Mice, Knockout, Extracellular matrix, Mice, MESH: Collagen, Myocyte, Myocytes, Cardiac, MESH: Animals, Cells, Cultured, Ultrasonography, Mice, Knockout, 0303 health sciences, MESH: Sarcomeres, 030302 biochemistry & molecular biology, Anatomy, Cell biology, medicine.anatomical_structure, MESH: Models, Animal, Models, Animal, Collagen, MESH: Endothelium, Vascular, MESH: Membrane Proteins, Cardiology and Cardiovascular Medicine, MESH: Cells, Cultured, Sarcomeres, animal structures, Ephrin-B1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Cell Communication, Dystroglycan, medicine, Animals, Ephrin, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Pressure overload, Basement membrane, MESH: Ephrin-B1, Cell Membrane, Erythropoietin-producing hepatocellular (Eph) receptor, Membrane Proteins, MESH: Male, Mice, Inbred C57BL, biology.protein, Endothelium, Vascular, sense organs, MESH: Cell Membrane
Abstract: Rationale: Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with tissue remodeling and architecture alterations. Objective: Eph/ephrin system constitutes a ubiquitous system coordinating cellular communications which recently emerged as a major regulator in adult organs. We examined if eph/ephrin could participate in cardiac tissue cyto-organization. Methods and Results: We reported the expression of cardiac ephrin-B1 in both endothelial cells and for the first time in CMs where ephrin-B1 localized specifically at the lateral membrane. Ephrin-B1 knock-out (KO) mice progressively developed cardiac tissue disorganization with loss of adult CM rod-shape and sarcomeric and intercalated disk structural disorganization confirmed in CM-specific ephrin-B1 KO mice. CMs lateral membrane exhibited abnormal structure by electron microscopy and notably increased stiffness by atomic force microscopy. In wild-type CMs, ephrin-B1 interacted with claudin-5/ZO-1 complex at the lateral membrane, whereas the complex disappeared in KO/CM-specific ephrin-B1 KO mice. Ephrin-B1 deficiency resulted in decreased mRNA expression of CM basement membrane components and disorganized fibrillar collagen matrix, independently of classical integrin/dystroglycan system. KO/CM-specific ephrin-B1 KO mice exhibited increased left ventricle diameter and delayed atrioventricular conduction. Under pressure overload stress, KO mice were prone to death and exhibited striking tissue disorganization. Finally, failing CMs displayed downregulated ephrin-B1/claudin-5 gene expression linearly related to the ejection fraction. Conclusions: Ephrin-B1 is necessary for cardiac tissue architecture cohesion by stabilizing the adult CM morphology through regulation of its lateral membrane. Because decreased ephrin-B1 is associated with molecular/functional cardiac defects, it could represent a new actor in the transition toward heart failure.
Published: 2012

9. Calcium carbonate precipitation by anoxygenic phototrophic bacteria

Author: Irina Bundeleva, Pascale Bénézeth, E. I. Kompantseva, Liudmila S. Shirokova, Oleg S. Pokrovsky, Stéphanie Balor, Géosciences Environnement Toulouse (GET), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Institute of Ecological Problems of the Northern Regions, Russian Academy of Sciences [Moscow] (RAS), Winogradsky Institute of Microbiology, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Supports from GRASP project (MRTNCT-2006- 035868), LIA 'LEAGE', and grants of Russian Federation FCP 'Kadry' 2011-1.5-505-008 and 'Origin and Evolution of the Biosphere' (Russian Academy of Sciences)., Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mineralogy, Precipitation, Biology, 010502 geochemistry & geophysics, 01 natural sciences, 7. Clean energy, 03 medical and health sciences, chemistry.chemical_compound, [SDU.STU.GC]Sciences of the Universe [physics]/Earth Sciences/Geochemistry, Geochemistry and Petrology, Vaterite, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Calcite, 0303 health sciences, 030306 microbiology, Precipitation (chemistry), Geology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anoxygenic photosynthesis, Anoxygenic phototrophic bacteria, Monohydrocalcite, Kinetics, chemistry, [SDU]Sciences of the Universe [physics], 13. Climate action, Environmental chemistry, Carbonate, Microbiologically induced calcite precipitation, Biomineralization
Abstract: 16 pages; International audience; Carbonate biomineralization is considered as one of the main natural processes controlling CO2 levels in the atmosphere both in the past and at present time. In contrast to extensive studies of cyanobacterial calcification, biomineralization of anoxygenic phototrophic bacteria (APB) remained largely underestimated, despite their potentially important role on CaCO3 precipitation in the biomats, notably in the past. Haloalcaliphilic Rhodovulum steppense A-20s and halophilic neutrophilic Rhodovulum sp. S-17-65 were examined with respect to their ability to precipitate CaCO3 under controlled laboratory conditions. To characterize the link between the rate of bacterial growth (biomass production) and the rate of CaCO3 precipitation, batch kinetic experiments with live, dead and inactivated bacteria both in nutrient solution and in inert electrolyte were performed and produced precipitates were examined by SEM, TEM and XRD techniques. Active strains A-20s and S-17-65 precipitated calcite from initially supersaturated solutions (Ωcalcite = 10 to 40) via increasing Ωcalcite to 80–120 before the precipitation. The amount of precipitated CaCO3 (mole) was directly correlated with the amount of organic C in bacterial biomass produced with a slope of dependence ranging from 0.3 to 0.6 and from 0.1 to 0.3 for A-20s and S-17-65, respectively, depending on the initial solution composition. For both bacterial strains, only live actively photosynthetizing bacteria were capable of effectively decreasing Ca concentration and form CaCO3 with apparent bulk precipitation rates ranging from 0.001 to 0.0150 mmol/h at 10–20 gwet/L of biomass, similar to rates reported for other bacteria. SEM and XRD analyses of precipitates reveal the dominance of calcite with some amount of vaterite and monohydrocalcite forming spheres up to 100 μm diameter. The TEM analysis of bacterial suspension at the end of precipitation experiments did not demonstrate the presence of CaCO3 at the surface or in the vicinity of live cells. This suggests the existence of certain cell protection mechanism against carbonate precipitation at the cell surface. Given the lower efficiency of photoheterotrophic APB, compared to photoautotrophic cyanobacteria, to precipitate CaCO3 in natural conditions, it is possible that the overall potential of phototrophic community to form massive carbonate deposits was strongly limited before the appearance of oxygenic phototrophs.
Published: 2012

10. Synthesis of New Alkylaminooxysterols with Potent Cell Differentiating Activities: Identification of Leads for the Treatment of Cancer and Neurodegenerative Diseases

Author: Bruno Payré, Michael R. Paillasse, Marc Poirot, Sandrine Silvente-Poirot, Philippe de Medina, Département de chimie, Affichem, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Poirot, Marc, and Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul)
Subjects: Spermidine, Cellular differentiation, Cell, MESH: Neurodegenerative Diseases, Mice, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Drug Discovery, MESH: Animals, MESH: Neoplasms, Amines, Cytotoxicity, 0303 health sciences, MESH: Amines, Cell Differentiation, Neurodegenerative Diseases, Stereoisomerism, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Sterols, medicine.anatomical_structure, MESH: Cell Survival, Biochemistry, 030220 oncology & carcinogenesis, Molecular Medicine, MESH: Cell Differentiation, MESH: Cell Line, Tumor, Neurite, Cell Survival, MESH: Dendrites, 03 medical and health sciences, MESH: Drug Discovery, Cell Line, Tumor, medicine, Animals, Humans, MESH: Mice, 030304 developmental biology, MESH: Humans, Cancer, Dendrites, medicine.disease, MESH: Stereoisomerism, chemistry, Cell culture, MESH: Sterols, Putrescine, Cholestanols
Abstract: International audience; We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-hydroxyl-6beta-aminoalkylsterols is presented. Compounds were first screened for dendrite outgrowth and cytotoxicity in vitro, and two leads were selected and further characterized. 5alpha-Hydroxy-6beta-[2-(1H-imidazol-4-yl)ethylamino]cholestan-3beta-ol, called dendrogenin A, induced growth control, differentiation, and the death of tumor cell lines representative of various cancers including metastatic melanoma and breast cancer. 5alpha-Hydroxy-6beta-[3-(4-aminobutylamino)propylamino]cholest-7-en-3beta-ol, called dendrogenin B, induced neurite outgrowth on various cell lines, neuronal differentiation in pluripotent cells, and survival of normal neurones at nanomolar concentrations. In summary, we report that two new alkylaminooxysterols, dendrogenin A and dendrogenin B, are the first members of a class of compounds that induce cell differentiation at nanomolar concentrations and represent promising new leads for the treatment of cancer or neurodegenerative diseases.
Published: 2009

11. Escherichia coli under Ionic Silver Stress: An Integrative Approach to Explore Transcriptional, Physiological and Biochemical Responses

Author: Frédéric Jamme, Isabelle Fourquaux, Claire Saulou-Bérion, Laurence Girbal, Muriel Cocaign-Bousquet, Muriel Mercier-Bonin, Ignacio González, Jean-Nicolas Audinot, Brice Enjalbert, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Materials Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology (LIST), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Synchrotron SOLEIL, ANR-07-BLAN-0196,BIOPLEASURE,Plasma - surface engineering for biofilm prevention(2007), Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Girbal, Laurence
Subjects: Silver, Transcription, Genetic, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], lcsh:Medicine, Biology, medicine.disease_cause, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, Ribosomal protein, Stress, Physiological, E. Coli, Gene expression, medicine, Extracellular, lcsh:Science, Escherichia coli, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Escherichia coli K12, Ag nanoparticles, 030306 microbiology, Escherichia coli Proteins, lcsh:R, Gene Expression Regulation, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Silver nitrate, medicine.anatomical_structure, chemistry, Biochemistry, Silver Nitrate, lcsh:Q, escherichia coli, Intracellular, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an], Research Article
Abstract: International audience; For a better understanding of the systemic effect of sub-lethal micromolar concentrations of ionic silver on Escherichia coli, we performed a multi-level characterization of cells under Ag +-mediated stress using an integrative biology approach combining physiological, biochemical and transcriptomic data. Physiological parameters, namely bacterial growth and survival after Ag + exposure, were first quantified and related to the accumulation of intracel-lular silver, probed for the first time by nano secondary ion mass spectroscopy at sub-micrometer lateral resolution. Modifications in E. coli biochemical composition were evaluated under Ag +-mediated stress by in situ synchrotron Fourier-transform infrared micro-spectroscopy and a comprehensive transcriptome response was also determined. Using multivariate statistics, correlations between the physiological parameters, the extracellular concentration of AgNO 3 and the intracellular silver content, gene expression profiles and micro-spectroscopic data were investigated. We identified Ag +-dependent regulation of gene expression required for growth (e.g. transporter genes, transcriptional regulators, ribo-somal proteins), for ionic silver transport and detoxification (e.g. copA, cueO, mgtA, nhaR) and for coping with various types of stress (dnaK, pspA, metA,R, oxidoreductase genes). The silver-induced shortening of the acyl chain of fatty acids, mostly encountered in cell membrane, was highlighted by microspectroscopy and correlated with the down-regulated expression of genes involved in fatty acid transport (fadL) and synthesis/modification of lipid A (lpxA and arnA). The increase in the disordered secondary structure of proteins in the presence of Ag + was assessed through the conformational shift shown for amides I and II, and further correlated with the up-regulated expression of peptidase (hfq) and chaperone (dnaJ), and regulation of transpeptidase expression (ycfS and ycbB). Interestingly, as these transpeptidases act on the structural integrity of the cell wall, regulation of their expression may explain the morphological damage reported under Ag+-mediated stress. This result clearly demonstrates that the cell membrane is a key target of ionic silver.
Published: 2015

12. Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response

Author: Nicole Malet, Matthias P. Wymann, Laurent O. Martinez, Natalia F. Smirnova, Emilio Hirsch, Abdelhadi Saoudi, Nathalie Vaillant, Christophe Pedros, Dominique Goudounèche, Alain-Pierre Gadeau, Stéphanie Gayral, Denis Calise, Muriel Laffargue, Gervaise Loirand, Sahar Kassem, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement /u563 : Lipoproteines et Mediateurs Lipidiques, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de micro-chirurgie, Laboratoire de Micro Chirurgie, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Biochemistry and Genetics, Università degli studi di Torino (UNITO), Adaptation cardiovasculaire à l'ischemie, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Neointima, Male, medicine.medical_specialty, Intimal hyperplasia, medicine.medical_treatment, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 030204 cardiovascular system & hematology, Vascular occlusion, Article, Rats, Sprague-Dawley, 03 medical and health sciences, Mice, 0302 clinical medicine, Restenosis, Internal medicine, Quinoxalines, medicine, Immunology and Allergy, CXCL10, Animals, Class Ib Phosphatidylinositol 3-Kinase, Enzyme Inhibitors, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Phosphoinositide-3 Kinase Inhibitors, Mice, Knockout, 0303 health sciences, business.industry, hemic and immune systems, Hyperplasia, Th1 Cells, medicine.disease, Arterial occlusion, 3. Good health, Surgery, Rats, Femoral Artery, Mice, Inbred C57BL, Endocrinology, Cytokine, Gene Targeting, Thiazolidinediones, medicine.symptom, Inflammation Mediators, business, Carotid Artery Injuries
Abstract: PI3Kγ plays a major role in the initiation and progression of intimal hyperplasia by specifically modulating Th1 cytokines leading to CXCL10 and RANTES production by smooth muscle cells., Interventional strategies to treat atherosclerosis, such as transluminal angioplasty and stent implantation, often cause vascular injury. This leads to intimal hyperplasia (IH) formation that induces inflammatory and fibroproliferative processes and ultimately restenosis. We show that phosphoinositide 3-kinase γ (PI3Kγ) is a key player in IH formation and is a valid therapeutic target in its prevention/treatment. PI3Kγ-deficient mice and mice expressing catalytically inactive PI3Kγ (PI3Kγ KD) showed reduced arterial occlusion and accumulation of monocytes and T cells around sites of vascular lesion. The transfer of PI3Kγ KD CD4+ T cells into Rag2-deficient mice greatly reduced vascular occlusion compared with WT cells, clearly demonstrating the involvement of PI3Kγ in CD4+ T cells during IH formation. In addition we found that IH is associated with increased levels of Th1 and Th17 cytokines. A specific decrease in the Th1 response was observed in the absence of PI3Kγ activity, leading to decreased CXCL10 and RANTES production by smooth muscle cells. Finally, we show that treatment with the PI3Kγ inhibitor AS-605240 is sufficient to decrease IH in both mouse and rat models, reinforcing the therapeutic potential of PI3Kγ inhibition. Altogether, these findings demonstrate a new role for PI3Kγ activity in Th1-controlled IH development.
Published: 2014

13. Targeting a G-Protein-Coupled Receptor Overexpressed in Endocrine Tumors by Magnetic Nanoparticles To Induce Cell Death

Author: Darine El Hajj Diab, Julian Carrey, Etienne Meunier, Reasmey P. Tan, Bruno Payré, Bernard Pipy, Véronique Gigoux, Vincent Connord, Pascal Clerc, Daniel Fourmy, Michel Gougeon, Claire Sanchez, Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR50, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), 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-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Réceptologie et Ciblage Thérapeutique en Cancérologie (RCTC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INSERM grant no. PC201310, European Project: 262943,EC:FP7:NMP,FP7-NMP-2010-LARGE-4,MULTIFUN(2011), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National des Sciences Appliquées de Toulouse - INSA (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Centre de Microscopie Electronique Appliquée à la Biologie - CMEAB (Toulouse, france), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Matériaux, media_common.quotation_subject, General Physics and Astronomy, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ferric Compounds, Cell Line, Receptors, G-Protein-Coupled, Magnetics, Mice, 03 medical and health sciences, chemistry.chemical_compound, Iron oxide nanoparticles, Cell surface receptor, Endocrine Gland Neoplasms, Gastrins, Endocrine tumors, Animals, Humans, General Materials Science, Epidermal growth factor receptor, Internalization, Receptor, 030304 developmental biology, media_common, Dynamin, G protein-coupled receptor, 0303 health sciences, Alternating magnetic field, Cell Death, biology, Macrophages, Lysosomal cell death pathways, General Engineering, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Cholecystokinin-2 receptor, Ingénierie biomédicale, Cell biology, HEK293 Cells, chemistry, Biochemistry, Apoptosis, biology.protein, Nanoparticles, 0210 nano-technology, Intracellular trafficking
Abstract: International audience; Nanotherapy using targeted magnetic nanoparticles grafted with peptidic ligands of receptors overexpressed in cancers is a promising therapeutic strategy. However, nanoconjugation of peptides can dramatically affect their properties with respect to receptor recognition, mechanism of internalization, intracellular trafficking, and fate. Furthermore, investigations are needed to better understand the mechanism whereby application of an alternating magnetic field to cells containing targeted nanoparticles induces cell death. Here, we designed a nanoplatform (termed MG-IONP-DY647) composed of an iron oxide nanocrystal decorated with a ligand of a G-protein coupled receptor, the cholecystokinin-2 receptor (CCK2R) that is overexpressed in several malignant cancers. MG-IONP-DY647 did not stimulate inflammasome of Raw 264.7 macrophages. They recognized cells expressing CCK2R with a high specificity, subsequently internalized via a mechanism involving recruitment of β-arrestins, clathrin-coated pits, and dynamin and were directed to lysosomes. Binding and internalization of MG-IONP-DY647 were dependent on the density of the ligand at the nanoparticle surface and were slowed down relative to free ligand. Trafficking of CCK2R internalized with the nanoparticles was slightly modified relative to CCK2R internalized in response to free ligand. Application of an alternating magnetic field to cells containing MG-IONP-DY647 induced apoptosis and cell death through a lysosomal death pathway, demonstrating that cell death is triggered even though nanoparticles of low thermal power are internalized in minute amounts by the cells. Together with pioneer findings using iron oxide nanoparticles targeting tumoral cells expressing epidermal growth factor receptor, these data represent a solid basis for future studies aiming at establishing the proof-of-concept of nanotherapy of cancers using ligand-grafted magnetic nanoparticles specifically internalized via cell surface receptors.
Published: 2014

14. 5,6-Epoxy-cholesterols contribute to the anticancer pharmacology of Tamoxifen in breast cancer cells

Author: Gregory, Segala, Medina, P. D., De Medina, P., Philippe Medina, D. E., Iuliano, Luigi, Zerbinati, Chiara, Paillasse, Michael R., Emmanuel, Noguer, Florence, Dalenc, Bruno, Payre, Craig Jordan, V., Michel, Record, Sandrine Silvente Poirot, Marc, Poirot, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Université Fédérale Toulouse Midi-Pyrénées, Affichem, Department of Medico-Surgical Sciences & Biotechnologies, Università degli Studi di Roma 'La Sapienza' [Rome], Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Lombardi comprehensive cancer center, Georgetown University Medical Center, Sterol metabolism and therapeutic innovations in oncology, CRLCC Institut Claudius Regaud-CRLCC Institut Claudius Regaud-Université Toulouse III - Paul Sabatier (UT3), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Poirot, Marc, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul)
Subjects: Selective Estrogen Receptor Modulators, aebs, Pyrrolidines, Oxysterol, breast cancer, cheh, sulfation, cholesterol epoxide, Antineoplastic Agents, Breast Neoplasms, Pharmacology, Ligands, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Estrogen Receptor Modulators, SULT2B1, Cell Line, Tumor, medicine, Humans, Liver X receptor, Receptor, Triglycerides, 030304 developmental biology, Liver X Receptors, Epoxide Hydrolases, 0303 health sciences, Binding Sites, Chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Antiestrogen, Orphan Nuclear Receptors, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Tamoxifen, Cholesterol, Selective estrogen receptor modulator, 030220 oncology & carcinogenesis, Female, Signal transduction, Sulfotransferases, Reactive Oxygen Species, Oxidation-Reduction, medicine.drug
Abstract: International audience; Tamoxifen (Tam) is a selective estrogen receptor modulator (SERM) that remains one of the major drugs used in the hormonotherapy of breast cancer (BC). In addition to its SERM activity, we recently showed that the oxidative metabolism of cholesterol plays a role in its anticancer pharmacology. We established that these effects were not regulated by the ER but by the microsomal antiestrogen binding site/cholesterol-5,6-epoxide hydrolase complex (AEBS/ChEH). The present study aimed to identify the oxysterols that are produced under Tam treatment and to define their mechanisms of action. Tam and PBPE (a selective AEBS/ChEH ligand) stimulated the production and the accumulation of 5,6α-epoxy-cholesterol (5,6α-EC), 5,6α-epoxy-cholesterol-3β-sulfate (5,6-ECS), 5,6β-epoxy-cholesterol (5,6β-EC) in MCF-7 cells through a ROS-dependent mechanism, by inhibiting ChEH and inducing sulfation of 5,6α-EC by SULT2B1b. We showed that only 5,6α-EC was responsible for the induction of triacylglycerol (TAG) biosynthesis by Tam and PBPE, through the modulation of the oxysterol receptor LXRβ. The cytotoxicity mediated by Tam and PBPE was triggered by 5,6β-EC through an LXRβ-independent route and by 5,6-ECS through an LXRβ-dependent mechanism. The importance of SULT2B1b was confirmed by its ectopic expression in the SULT2B1b(-) MDA-MB-231 cells, which became sensitive to 5,6α-EC, Tam or PBPE at a comparable level to MCF-7 cells. This study established that 5,6-EC metabolites contribute to the anticancer pharmacology of Tam and highlights a novel signaling pathway that points to a rationale for re-sensitizing BC cells to Tam and AEBS/ChEH ligands.
Published: 2013

15. Synchrotron FTIR microspectroscopy of Escherichia coli at single-cell scale under silver-induced stress conditions

Author: Claire Saulou, Muriel Mercier-Bonin, Isabelle Fourquaux, Paul Dumas, Claude Maranges, Frédéric Jamme, Muriel Cocaign-Bousquet, Laurence Girbal, Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The authors gratefully acknowledge the 'BioPleasure' project of the Research National Agency (ANR-07-BLAN-0196-01) for funding., The research described in this paper was performed at the French national synchrotron facility SOLEIL (Gif-sur- Yvette, France), using the SMIS beamline (proposal no 20090556)., ANR-07-BLAN-0196,BIOPLEASURE,Plasma - surface engineering for biofilm prevention(2007), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées (INSA), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
Subjects: In situ, Analytical chemistry, medicine.disease_cause, Biochemistry, Analytical Chemistry, 03 medical and health sciences, Stress, Physiological, Spectroscopy, Fourier Transform Infrared, medicine, Escherichia coli, Fourier transform infrared spectroscopy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein secondary structure, 030304 developmental biology, 0303 health sciences, biology, Ionic silver, 030306 microbiology, Chemistry, Synchrotron FTIR-ATR microspectroscopy, Single-cell scale, [CHIM.MATE]Chemical Sciences/Material chemistry, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Antibacterial effect, Transmission electron microscopy, Attenuated total reflection, Ultrastructure, Biophysics, Silver Nitrate, Single-Cell Analysis, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Synchrotrons, Bacteria
Abstract: International audience; The present work was focused on elucidating biochemical changes in the model bacterium Escherichia coli exposed to ionic silver mediated stress, at a single-cell scale. In order to achieve this, in situ synchrotron Fourier-transform infrared (sFTIR) microspectroscopy was performed, for the first time, on individual cells by attenuated total reflectance (ATR) combined with the use of zinc-selenide hemisphere for high spatial resolution. In a first part, the potential of the method was evaluated on bacteria subjected to a lethal 100 μM AgNO3 concentration for 2 h compared to untreated 100 % viable cells. Differences in cell composition were assessed for the C–H stretching and protein spectral regions, indicating that the inhibitory action was targeted against both fatty acids and proteins. Transmission electron microscopy (TEM) confirmed morphological damages of the cell ultrastructure. The relevance of ATR-sFTIR microspectroscopy for highlighting the heterogeneity in Ag+-mediated effects within a given bacterial population was also pointed out. In a second part, cells were exposed to sub-lethal Ag+ concentrations (
Published: 2013

16. Zeta potential of anoxygenic phototrophic bacteria and Ca adsorption at the cell surface: possible implications for cell protection from CaCO3 precipitation in alkaline solutions

Author: Pascale Bénézeth, E. I. Kompantseva, Liudmila S. Shirokova, Oleg S. Pokrovsky, Irina Bundeleva, Stéphanie Balor, Géosciences Environnement Toulouse (GET), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Institute of Ecological Problems of the Northern Regions, Russian Academy of Sciences [Moscow] (RAS), Winogradsky Institute of Microbiology, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Work supported by the GRASP project (MRTNCT-2006-035868), INSU program ‘‘INTERVIE’’ and partially by RFBR (Project No. 07-04-00651a) and the program ‘‘Origin and Evolution of the Biosphere’’ (Russian Academy of Sciences)., Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Electrophoresis, Rhodovulum, Rhodovulum sp, Surface Properties, Bicarbonate, Inorganic chemistry, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, chemistry.chemical_element, Calcium, Calcium Carbonate, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Colloid and Surface Chemistry, Adsorption, [SDU.STU.GC]Sciences of the Universe [physics]/Earth Sciences/Geochemistry, Zeta potential, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Chemistry, Calcite, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anoxygenic photosynthesis, Anoxygenic phototrophic bacteria, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Solutions, [SDU]Sciences of the Universe [physics], Ionic strength
Abstract: 10 pages; International audience; Electrophoretic mobility measurements and surface adsorption of Ca on living, inactivated, and heat-killed haloalkaliphilic Rhodovulum steppense, A-20s, and halophilic Rhodovulum sp., S-17-65 anoxygenic phototrophic bacteria (APB) cell surfaces were performed to determine the degree to which these bacteria metabolically control their surface potential equilibria. Zeta potential of both species was measured as a function of pH and ionic strength, calcium and bicarbonate concentrations. For both live APB in 0.1M NaCl, the zeta potential is close to zero at pH from 2.5 to 3 and decreases to -30 to -40 mV at pH of 5-8. In alkaline solutions, there is an unusual increase of zeta potential with a maximum value of -10 to -20 mV at a pH of 9-10.5. This increase of zeta potential in alkaline solutions is reduced by the presence of NaHCO(3) (up to 10 mM) and only slightly affected by the addition of equivalent amount of Ca. At the same time, for inactivated (exposure to NaN(3), a metabolic inhibitor) and heat-killed bacteria cells, the zeta potential was found to be stable (-30 to -60 mV, depending upon the ionic strength) between pH 5 and 11 without any increase in alkaline solutions. Adsorption of Ca ions on A-20s cells surface was more significant than that on S-17-65 cells and started at more acidic pHs, consistent with zeta potential measurements in the presence of 0.001-0.01 mol/L CaCl(2). Overall, these results indicate that APB can metabolically control their surface potential to electrostatically attract nutrients at alkaline pH, while rejecting/avoiding Ca ions to prevent CaCO(3) precipitation in the vicinity of cell surface and thus, cell incrustation.
Published: 2011

17. Ultrastructural changes in the third-stage, infective larvae of ruminant nematodes treated with sainfoin (Onobrychis viciifolia) extract

Author: S. Brunet, I. Fourquaux, Hervé Hoste, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-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-Université Fédérale Toulouse Midi-Pyrénées, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This work received financial support from the European Union as part of the Marie-Curie project 'Healthy Hay' (Project number: MRTN_CT-2006-035805). The financial support of the Region Midi-Pyrenees (contract 030121196) is also sincerely acknowledged. Special thanks are due to Dr. I. Mueller-Harvey of the University of Reading for helpful comments on the manuscript and to Mrs D. Goodfellow to revise the English version of the article.
Subjects: infective third-stage larvae, Plastic Embedding, Nematoda, 040301 veterinary sciences, parasitology, Cuticle, [SDV]Life Sciences [q-bio], Biology, 030308 mycology & parasitology, Microbiology, Specimen Handling, 0403 veterinary science, 03 medical and health sciences, Microscopy, Electron, Transmission, Ruminant, tannins, Botany, transmission electron microscopy, Animals, parasitic nematode, Anthelmintics, 0303 health sciences, Larva, Plant Extracts, Onobrychis viciifolia, Fabaceae, 04 agricultural and veterinary sciences, Microtomy, Ruminants, biology.organism_classification, In vitro, Infectious Diseases, Nematode, Proanthocyanidin, Ultrastructure, sainfoin (Onobrychis viciifolia)
Abstract: International audience; Plants rich in condensed tannins are an alternative to chemical anthelmintics to control gastrointestinal nematodes (GINs) in ruminants. Previous functional studies have shown that sainfoin extracts affect the two forms of infective larvae (L3), ensheathed and exsheathed. However, the mechanisms of action remain unknown. The aim of this study was thus to compare ultrastructural changes in ensheathed and exsheathed 13 of two GIN species after in vitro contact with sainfoin extracts using transmission electron microscopy. The main changes identified were an alteration of the hypodermis, the presence of numerous vesicles in the cytoplasm and degeneration and/or death of muscular and intestinal cells. The changes suggested similar and nonspecies-specific lesions in the two nematode species. Comparison of the modifications found in the ensheathed vs. exsheathed L3s revealed different locations of the main cellular changes depending on the larval form. It is hypothesized that these spatial differences in lesions are mainly influenced by the presence of the sheath which favors contact between the active compounds and either the cuticle or the digestive tract. Overall, our observations suggest that the functional changes observed in the biology of GIN Us after contact with sainfoin extracts are mediated through a direct mode of action, i.e. different interactions between the bioactive plant metabolites and the nematode structure depending on the route of contact.
Published: 2011

18. Endothelial estrogen receptor {alpha} plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion

Author: Françoise Lenfant, Ji Gao, Isabelle Remy-Jouet, Isabelle Fourquaux, Jean-Paul Henry, Christian Thuillez, Julie Favre, Audrey Billon-Galés, Vincent Richard, Jean-François Arnal, Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Simon, Marie Francoise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul)
Subjects: Time Factors, Vasodilator Agents, Estrogen receptor, Blood Pressure, Vasodilation, 030204 cardiovascular system & hematology, MESH: Mice, Knockout, MESH: Drug Implants, MESH: Dose-Response Relationship, Drug, Mice, 0302 clinical medicine, Heart Rate, MESH: Coronary Vessels, MESH: Animals, MESH: Endothelial Cells, Endothelial dysfunction, MESH: Heart Rate, MESH: Bone Marrow Transplantation, MESH: Estrogen Receptor alpha, Bone Marrow Transplantation, Drug Implants, Mice, Knockout, 0303 health sciences, Estradiol, Estrogen Replacement Therapy, MESH: Reactive Oxygen Species, MESH: Blood Pressure, Coronary Vessels, MESH: Myocardial Reperfusion Injury, medicine.anatomical_structure, MESH: Uterus, Female, MESH: Estradiol, Cardiology and Cardiovascular Medicine, MESH: Transplantation Chimera, medicine.medical_specialty, MESH: Myocardium, Endothelium, medicine.drug_class, Ovariectomy, Ischemia, MESH: Ovariectomy, Myocardial Reperfusion Injury, MESH: Vasodilation, 03 medical and health sciences, In vivo, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, MESH: Mice, 030304 developmental biology, Transplantation Chimera, Dose-Response Relationship, Drug, business.industry, Myocardium, Uterus, MESH: Time Factors, Estrogen Receptor alpha, Endothelial Cells, medicine.disease, MESH: Estrogen Replacement Therapy, MESH: Vasodilator Agents, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Estrogen, MESH: Disease Models, Animal, Reactive Oxygen Species, business, MESH: Female, Ex vivo
Abstract: Objective— To assess the coronary endothelial protective effects of 17β-estradiol (E2) and the role of estrogen receptor (ER) α in ischemia/reperfusion (I/R). Methods and Results— E2 exerts protective effects in cardiac I/R. However, the implication in vivo of the endothelium and the cellular targets of the anti-ischemic effects of E2 are unknown. Mice were subjected to I/R (30 minutes of I and 1 hour of R) in vivo, after which acetylcholine-induced relaxation of isolated coronary segments was assessed ex vivo. I/R induced a coronary endothelial dysfunction in untreated ovariectomized mice that was prevented by long-term treatment with E2 in wild-type, but not in ERα −/− , mice. Chimeric mice inactivated for ERα in the hematopoietic compartment remained protected by E2. Further inactivation of endothelial ERα abolished the protective action of E2 on coronary endothelial function in Tie2-Cre(+) ERα f/f mice. More importantly, E2 significantly limited infarct size in wild-type mice but not in mice deficient in endothelial ERα, even in the presence of hematopoietic ERα. Conclusion— Endothelial ERα plays a crucial role in the E2-induced prevention of endothelial dysfunction after I/R. To our knowledge, we demonstrate for the first time, by using unique genetically modified mice, that targeting endothelial protection per se can confer cardiomyocyte protection in I/R.
Published: 2010

19. Synchrotron FTIR microspectroscopy of the yeast Saccharomyces cerevisiae after exposure to plasma-deposited nanosilver-containing coating

Author: Claire Saulou, Isabelle Fourquaux, Muriel Mercier-Bonin, P. Dumas, C. Maranges, Patrice Raynaud, Bernard Despax, Frédéric Jamme, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées, LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Matériaux et Procédés Plasmas (LAPLACE-MPP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), The research described in this paper was performed at the French national synchrotron facility SOLEIL (Gif-sur-Yvette, France), using the SMIS beamline (proposal no 20060176)., ANR-07-BLAN-0196,BIOPLEASURE,Plasma - surface engineering for biofilm prevention(2007), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Antifungal effect, Antifungal Agents, Silver, Cell Survival, Surface Properties, Scanning electron microscope, Thin films, Analytical chemistry, Metal Nanoparticles, Nanoparticle, Infrared spectroscopy, 02 engineering and technology, Saccharomyces cerevisiae, Biochemistry, Silver nanoparticle, Analytical Chemistry, Biomaterials, Plasma, 03 medical and health sciences, Nanosilvercontaining coating, Biological samples, Microscopy, Electron, Transmission, X-ray photoelectron spectroscopy, Synchrotron FTIR microspectroscopy, Spectroscopy, Fourier Transform Infrared, IR spectroscopy/Raman spectroscopy, Fourier transform infrared spectroscopy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, 030304 developmental biology, 0303 health sciences, Nanocomposite, Chemistry, 021001 nanoscience & nanotechnology, Nanoparticles/ Nanotechnology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Transmission electron microscopy, Cold plasma, Interface/Surface analysis, 0210 nano-technology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Synchrotrons, Nuclear chemistry
Abstract: International audience; The present work was focused on elucidating changes in the model yeast Saccharomyces cerevisiae (cell composition, ultrastructure) after exposure to antimicrobial plasma-mediated nanocomposite films. In order to achieve this, a nanosilver-containing coating was deposited onto stainless steel using radiofrequency HMDSO plasma deposition, combined with simultaneous silver sputtering. X-ray photoelectron spectroscopy (XPS) confirmed the presence of silver nanoparticles embedded in an organo-silicon matrix. In addition, scanning electron microscopy (SEM) demonstrated the nanoparticle-based morphology of the deposited layer. The antifungal properties towards S. cerevisiae were established, since a 1.4 log reduction in viable counts was observed after a 24-h adhesion compared to control conditions with the matrix alone. Differences in cell composition after exposure to the nanosilver was assessed for the protein region using, for the first time, synchrotron Fourier-transform infrared (FTIR) microspectroscopy of single S. cerevisiae cells, through in situ mapping with sub-cellular spatial resolution. IR spectrum of yeast cells recovered after a 24-h adhesion to the nanosilver-containing coating revealed a significant downshift (20 cm −1) of the amide I peak at 1655 cm −1 , compared to freshly harvested cells. This lower band position, corresponding to a loss in α-helix structures, is indicative of the disordered secondary structures of proteins, due to the transition between active and inactive conformations under nanosilver-induced stress conditions. No significant effect on the nucleic acid region was detected. The inhibitory action of silver was targeted against both cell wall and intracellular proteins such as enzymes. Transmission electron microscopy (TEM) observations of the yeastultrastructure confirmed serious morphological and structural damages. A homogeneous protein-binding distribution of nanosilver all over the cell was assumed, since the presence of electron-dense silver clusters was detected not only on the cell surface but also within the cell. For control experiments with the organosilicon matrix alone, no antimicrobial effect was observed, which was consistent with synchrotron FTIR results and TEM observations.
Published: 2010

20. Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism

Author: P. De Medina, Marc Poirot, N Boubekeur, François Tercé, Bruno Payré, Justine Bertrand-Michel, Sandrine Silvente-Poirot, Département de chimie, Affichem, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Poirot, Marc, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul
Subjects: Pyrrolidines, Cellular differentiation, Apoptosis, Ligands, 0302 clinical medicine, MESH: Vitamin E, MESH: Cholesterol, Estrogen Receptor Modulators, Annexin, Tumor Cells, Cultured, MESH: Ligands, Vitamin E, skin and connective tissue diseases, 0303 health sciences, MESH: Reactive Oxygen Species, Cell Differentiation, MESH: Antineoplastic Agents, Hormonal, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Estrogen Receptor Modulators, 3. Good health, Cell biology, Mitochondria, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cholesterol, 030220 oncology & carcinogenesis, Female, MESH: Cell Differentiation, Programmed cell death, Antineoplastic Agents, Hormonal, MESH: Mitochondria, Breast Neoplasms, Biology, MESH: Ethylamines, 03 medical and health sciences, Autophagy, Ethylamines, Humans, MESH: Autophagy, MESH: Tumor Cells, Cultured, Binding site, Molecular Biology, 030304 developmental biology, Binding Sites, MESH: Humans, MESH: Pyrrolidines, MESH: Apoptosis, Cell Biology, Antiestrogen, Tamoxifen, MESH: Binding Sites, Cancer cell, MESH: Tamoxifen, Reactive Oxygen Species, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; We have recently reported that cytostatic concentrations of the microsomal antiestrogen-binding site (AEBS) ligands, such as PBPE (N-pyrrolidino-(phenylmethyphenoxy)-ethanamine,HCl) and tamoxifen, induced differentiation characteristics in breast cancer cells through the accumulation of post-lanosterol intermediates of cholesterol biosynthesis. We show here that exposure of MCF-7 (human breast adenocarcinoma cell line) cells to higher concentrations of AEBS ligands triggered active cell death and macroautophagy. Apoptosis was characterized by Annexin V binding, chromatin condensation, DNA laddering and disruption of the mitochondrial functions. We determined that cell death was sterol- and reactive oxygen species-dependent and was prevented by the antioxidant vitamin E. Macroautophagy was characterized by the accumulation of autophagic vacuoles, an increase in the expression of Beclin-1 and the stimulation of autophagic flux. We established that macroautophagy was sterol- and Beclin-1-dependent and was associated with cell survival rather than with cytotoxicity, as blockage of macroautophagy sensitized cells to AEBS ligands. These results show that the accumulation of sterols by AEBS ligands in MCF-7 cells induces apoptosis and macroautophagy. Collectively, these data support a therapeutic potential for selective AEBS ligands in breast cancer management and shows a mechanism that explains the induction of autophagy in MCF-7 cells by tamoxifen and other selective estrogen receptor modulators.
Published: 2009

21. Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human breast cancer cells through the modulation of cholesterol metabolism

Author: Isabelle Fourquaux, Philippe de Medina, Nadia Boubekeur, Bruno Payré, Sandrine Silvente-Poirot, Loubna Mhamdi, Marc Poirot, François Tercé, Justine Bertrand-Michel, Dominique Goudounèche, Michel Record, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Département de chimie, Affichem, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), 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), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poirot, Marc, Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, 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), and 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)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Cancer Research, Time Factors, Cellular differentiation, MESH: Flow Cytometry, Ligands, 0302 clinical medicine, MESH: Cholesterol, Estrogen Receptor Modulators, MESH: Ligands, 0303 health sciences, Cell Differentiation, Cell cycle, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Flow Cytometry, Milk Proteins, Lipids, MESH: Estrogen Receptor Modulators, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cholesterol, Oncology, Biochemistry, 030220 oncology & carcinogenesis, Intracellular, MESH: Cell Differentiation, MESH: Milk Proteins, MESH: Cell Line, Tumor, Breast Neoplasms, Biology, MESH: Microsomes, 03 medical and health sciences, Cell Line, Tumor, Microsomes, MESH: Cell Proliferation, Humans, Binding site, 030304 developmental biology, Cell Proliferation, Binding Sites, MESH: Humans, Cell growth, MESH: Time Factors, Antiestrogen, MESH: Lipids, Tamoxifen, MESH: Binding Sites, Cell culture, Cancer cell, Cancer research, MESH: Tamoxifen, MESH: Breast Neoplasms
Abstract: The microsomal antiestrogen-binding site (AEBS) is a high-affinity membranous binding site for the antitumor drug tamoxifen that selectively binds diphenylmethane derivatives of tamoxifen such as PBPE and mediates their antiproliferative properties. The AEBS is a hetero-oligomeric complex consisting of 3β-hydroxysterol-Δ8-Δ7-isomerase and 3β-hydroxysterol-Δ7-reductase. High-affinity AEBS ligands inhibit these enzymes leading to the massive intracellular accumulation of zymostenol or 7-dehydrocholesterol (DHC), thus linking AEBS binding to the modulation of cholesterol metabolism and growth control. The aim of the present study was to gain more insight into the control of breast cancer cell growth by AEBS ligands. We report that PBPE and tamoxifen treatment induced differentiation in human breast adenocarcinoma cells MCF-7 as indicated by the arrest of cells in the G0-G1 phase of the cell cycle, the increase in the cell volume, the accumulation and secretion of lipids, and a milk fat globule protein found in milk. These effects were observed with other AEBS ligands and with zymostenol and DHC. Vitamin E abrogates the induction of differentiation and reverses the control of cell growth produced by AEBS ligands, zymostenol, and DHC, showing the importance of the oxidative processes in this effect. AEBS ligands induced differentiation in estrogen receptor-negative mammary tumor cell lines SKBr-3 and MDA-MB-468 but with a lower efficiency than observed with MCF-7. Together, these data show that AEBS ligands exert an antiproliferative effect on mammary cancer cells by inducing cell differentiation and growth arrest and highlight the importance of cholesterol metabolism in these effects. [Mol Cancer Ther 2008;7(12):3707–18]
Published: 2008

22. Murine embryonic stem cell-derived pancreatic acinar cells recapitulate features of early pancreatic differentiation

Author: Mohammad Massumi, Selma A. Serra, Josep Lloreta, Fabien Delaspre, Miguel A. Valverde, Bruno Payré, Francisco X. Real, Stephen F. Konieczny, Pierre Savatier, Marlène Dufresne, Meritxell Rovira, Anouchka Skoudy, Cancer Research Program, Institut Municipal d' Investigacio Mèdica, Laboratory of Molecular Physiology and Channelopathies, Barcelona, Laboratory of Molecular Physiology and Channelopathies, Department de Patologia, Hospital del Mar, Universitat Pompeu Fabra [Barcelona] (UPF), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Biological Sciences [West Lafayette], Purdue University [West Lafayette], Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and Simon, Marie Francoise
Subjects: MESH: Cell Differentiation, MESH: Pancreatic Elastase, Cellular differentiation, [SDV]Life Sciences [q-bio], Embryoid body, Biology, MESH: Calcium Signaling, 03 medical and health sciences, 0302 clinical medicine, Directed differentiation, MESH: Microscopy, Immunoelectron, Pancreatic cancer, MESH: Basic Helix-Loop-Helix Transcription Factors, MESH: Gene Expression Regulation, Developmental, medicine, MESH: Amylases, MESH: Animals, MESH: Pancreas, Exocrine, MESH: Embryonic Stem Cells, Pancreatic elastase, MESH: Mice, 030304 developmental biology, 0303 health sciences, MESH: Cell Culture Techniques, MESH: Exocytosis, Hepatology, MESH: Transfection, MESH: Gene Expression Regulation, Enzymologic, MESH: Genes, Reporter, Gastroenterology, MESH: Transcription Factors, medicine.disease, Embryonic stem cell, Molecular biology, MESH: Carboxypeptidases A, [SDV] Life Sciences [q-bio], MESH: Carbachol, medicine.anatomical_structure, MESH: Chymotrypsinogen, Cell culture, 030220 oncology & carcinogenesis, MESH: Cholinergic Agonists, MESH: Cell Division, Pancreas, MESH: Cells, Cultured
Abstract: International audience; BACKGROUND & AIMS: Acinar cells constitute 90% of the pancreas epithelium, are polarized, and secrete digestive enzymes. These cells play a crucial role in pancreatitis and pancreatic cancer. However, there are limited models to study normal acinar cell differentiation in vitro. The aim of this work was to generate and characterize purified populations of pancreatic acinar cells from embryonic stem (ES) cells. METHODS: Reporter ES cells (Ela-pur) were generated that stably expressed both beta-galactosidase and puromycin resistance genes under the control of the elastase I promoter. Directed differentiation was achieved by incubation with conditioned media of cultured fetal pancreatic rudiments and adenoviral-mediated co-expression of p48/Ptf1a and Mist1, 2 basic helix-loop-helix transcription factors crucial for normal pancreatic acinar development and differentiation. RESULTS: Selected cells expressed multiple markers of acinar cells, including digestive enzymes and proteins of the secretory pathway, indicating activation of a coordinated differentiation program. The genes coding for digestive enzymes were not regulated as a single module, thus recapitulating what occurs during in vivo pancreatic development. The generated cells displayed transient agonist-induced Ca(2+) mobilization and showed a typical response to physiologic concentrations of secretagogues, including enzyme synthesis and secretion. Importantly, these effects did not imply the acquisition of a mixed acinar-ductal phenotype. CONCLUSIONS: These studies allow the generation of almost pure acinar-like cells from ES cells, providing a normal cell-based model for the study of the acinar differentiation program in vitro.
Published: 2008

23. Mycobacterial lipomannan induces granuloma macrophage fusion via a TLR2-dependent, ADAM9- and beta1 integrin-mediated pathway

Author: Martine Gilleron, Jérôme Nigou, Guillaume Lay, Laurent Kremer, Laure Botella, Marie-Pierre Puissegur, Bernard Mari, Yann Guérardel, Frédéric Altare, Pascal Barbry, Jean-Luc Duteyrat, Hedia Marrakchi, Germain Puzo, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Antigens, CD29, Lipopolysaccharides, MESH: Granuloma, Cellular differentiation, [SDV]Life Sciences [q-bio], Giant Cells, MESH: Giant Cells, Cell Fusion, 0302 clinical medicine, hemic and lymphatic diseases, Macrophage fusion, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, 0303 health sciences, Cell fusion, Granuloma, Integrin beta1, MESH: Toll-Like Receptor 2, Cell Differentiation, 3. Good health, Cell biology, MESH: Membrane Proteins, MESH: Cells, Cultured, MESH: ADAM Proteins, MESH: Cell Differentiation, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Proinflammatory cytokine, Mycobacterium, 03 medical and health sciences, MESH: Bacterial Capsules, medicine, MESH: Mycobacterium, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Bacterial Capsules, 030304 developmental biology, Lipomannan, Lipoarabinomannan, MESH: Humans, Macrophages, MESH: Macrophages, Membrane Proteins, medicine.disease, Toll-Like Receptor 2, ADAM Proteins, Giant cell, MESH: Cell Fusion, MESH: Lipopolysaccharides, 030215 immunology
Abstract: Tuberculous granulomas are the sites of interaction between the host response and the tubercle bacilli within infected individuals. They mainly consist of organized aggregations of lymphocytes and macrophages (Mf). A predominant role of mycobacterial envelope glycolipids in granulomas formation has been recently emphasized, yet the signaling events interfering with granuloma cell differentiation remain elusive. To decipher this molecular machinery, we have recently developed an in vitro human model of mycobacterial granulomas. In this study, we provide evidence that the mycobacterial proinflammatory phosphatidyl-myo-inositol mannosides and lipomannans (LM), as well as the anti-inflammatory lipoarabinomannan induce granuloma formation, yet only the proinflammatory glycolipids induce the fusion of granuloma Mf into multinucleated giant cells (MGC). We also demonstrate that LM induces large MGC resembling those found in vivo within the granulomas of tuberculosis patients, and that this process is mediated by TLR2 and is dependent on the β1 integrin/ADAM9 cell fusion machinery. Our results demonstrate for the first time that the Mf differentiation stage specifically occurring within granulomatous structures (i.e., MGC formation) is triggered by mycobacterial envelope glycolipids, which are capable of inducing the cell fusion machinery. This provides the first characterization of the ontogeny of human granuloma MGC, thus resulting in a direct modulation by a particular mycobacterial envelope glycolipid of the differentiation process of granuloma Mf.
Published: 2007

24. Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity

Author: Sylvain Pitarque, Jean-Louis Herrmann, Douglas B. Young, Olivier Schwartz, Germain Puzo, Jérôme Nigou, Philippe H. Lagrange, Mary Jackson, Olivier Neyrolles, François Lecointe, Bruno Payré, Brigitte Gicquel, Graham R. Stewart, Jean-Luc Duteyrat, Gilles Marchal, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de microbiologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et epidémiologie moléculaire des infections microbiennes (EA_3510), Université Paris Diderot - Paris 7 (UPD7), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris], MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This research project was co-financed by the European Commission, within the Sixth Framework Programme (contract no. LSHP-CT-2003-503367), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Génétique mycobactérienne, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Tuberculosis, mycobacteria, dendritic cell, [SDV]Life Sciences [q-bio], dendritic-cell-specific intercellular molecule-3-grabbing non-integrin (DC-SIGN), Receptors, Cell Surface, Biology, Biochemistry, Bacterial Adhesion, Microbiology, Substrate Specificity, Mycobacterium tuberculosis, 03 medical and health sciences, Immune system, Antigen, Species Specificity, medicine, Humans, Lectins, C-Type, Molecular Biology, 030304 developmental biology, 0303 health sciences, Lipoarabinomannan, Lipomannan, 030302 biochemistry & molecular biology, Cell Biology, Dendritic cell, medicine.disease, biology.organism_classification, 3. Good health, DC-SIGN, tuberculosis, biology.protein, lipoarabinomannan, Cell Adhesion Molecules, HeLa Cells, Protein Binding, Research Article
Abstract: International audience; Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central to anti-mycobacterial immunity. We have previously shown that M. tuberculosis binds to human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, and we have suggested that DC-SIGN may discriminate between mycobacterial species through recognition of the mannose-capping residues on the lipoglycan lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and slow-growing Mycobacterium species, we provide further evidence that mycobacteria recognition by DC-SIGN may be restricted to species of the M. tuberculosis complex. Fine analyses of the lipoarabinomannan molecules purified from these species show that the structure and amount of these molecules alone cannot account for such a preferential recognition. We propose that M. tuberculosis recognition by DC-SIGN relies on both a potential difference of accessibility of lipoarabinomannan in its envelope and, more probably, on the binding of additional ligands, possibly including lipomannan, mannose-capped arabinomannan, as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich antigen)] glycoproteins. Altogether, our results reveal that the molecular basis of M. tuberculosis binding to DC-SIGN is more complicated than previously thought and provides further insight into the mechanisms of M. tuberculosis recognition by the immune system.
Published: 2005

25. Tamoxifen is a potent inhibitor of cholesterol esterification and prevents the formation of foam cells

Author: José Bernad, Bruno Payré, Gilles Favre, Marc Poirot, Bernard Pipy, Philippe de Medina, Isabelle Bosser, Jean-Charles Faye, Sandrine Silvente-Poirot, Poirot, Marc, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de la Signalisation et de la Différenciation des Macrophages, Institution Louis Bugnard, Département de chimie, Affichem, Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul)
Subjects: Male, MESH: Lipoproteins, LDL, Estrogen receptor, MESH: Rats, Sprague-Dawley, Pharmacology, MESH: Research Support, Non-U.S. Gov't, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, MESH: Cholesterol, MESH: Animals, Receptor, Cells, Cultured, Foam cell, 0303 health sciences, Chemistry, Estrogen Antagonists, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Lipoproteins, LDL, Cholesterol, Receptors, Estrogen, Selective estrogen receptor modulator, 030220 oncology & carcinogenesis, Molecular Medicine, MESH: Receptors, Estrogen, MESH: Stero, Cholesterol Esters, Pharmacophore, MESH: Macrophages, Peritoneal, hormones, hormone substitutes, and hormone antagonists, medicine.drug, MESH: Cells, Cultured, MESH: Esterification, medicine.medical_specialty, MESH: Rats, MESH: Foam Cells, MESH: Estrogen Antagonists, 03 medical and health sciences, Structure-Activity Relationship, Internal medicine, medicine, Animals, Humans, 030304 developmental biology, MESH: Humans, Esterification, MESH: Male, Rats, Tamoxifen, Endocrinology, MESH: Cholesterol Esters, Microsome, Macrophages, Peritoneal, Foam Cells, Sterol O-Acyltransferase
Abstract: Tamoxifen is a selective estrogen receptor modulator (SERM) used for the treatment and prevention of breast cancer. Tamoxifen has been reported to protect against the progression of coronary artery diseases in human and different atherosclerosis animal models by blocking the appearance of the atheromatous plaque. However, the molecular mechanism of this effect remains unknown. Acyl-CoA:cholesterol acyl transferase (ACAT) catalyzes the biosynthesis of cholesteryl esters, which are the major lipids found in the atheromatous plaque. In this paper we have tested whether ACAT might be inhibited by tamoxifen. We show, using molecular modeling, that tamoxifen displays three-dimensional structural homology with Sah 58-035 (3-[decyldimethylsilyl]-N-[2-(4-methylphenyl)-1-phenylethyl]-propanamide), a prototypical inhibitor of ACAT. We report that tamoxifen inhibits ACAT in a concentration-dependent manner on rat liver microsomal extract. We show that the presence on estrogen receptor ligands of a backbone isosteric to the diphenyl ethane backbone of Sah 58-035 constitutes a pharmacophore for ACAT inhibition. More importantly, tamoxifen was able to inhibit ACAT on intact macrophages stimulated with acetylated low-density lipoproteins and blocked the formation of foam cells, a step that precedes the formation of the atheromatous plaque. This work constitutes the first evidence that tamoxifen is an inhibitor of ACAT and foam cell formation at therapeutic doses and that this may account for its atheroprotective action.
Published: 2003

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25 results on '"Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB)"'

1. Spatial localization and binding of the probiotic Lactobacillus farciminis to the rat intestinal mucosa: influence of chronic stress

2. Cold helium plasma jet does not stimulate collagen remodeling in a 3D human dermal substitute

3. Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties

4. Uptake, fate, and gut toxicity of perfluorooctanoic acid (PFOA) in vitro

5. Structure and biological activities of a hexosamine-rich cell wall polysaccharide isolated from the probiotic Lactobacillus farciminis

6. Pectin Demethylesterification Generates Platforms that Anchor Peroxidases to Remodel Plant Cell Wall Domains

7. Direct and indirect effects of bioactive tannin-rich tropical and temperate legumes against nematode infections

8. Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

9. Calcium carbonate precipitation by anoxygenic phototrophic bacteria

10. Synthesis of New Alkylaminooxysterols with Potent Cell Differentiating Activities: Identification of Leads for the Treatment of Cancer and Neurodegenerative Diseases

11. Escherichia coli under Ionic Silver Stress: An Integrative Approach to Explore Transcriptional, Physiological and Biochemical Responses

12. Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response

13. Targeting a G-Protein-Coupled Receptor Overexpressed in Endocrine Tumors by Magnetic Nanoparticles To Induce Cell Death

14. 5,6-Epoxy-cholesterols contribute to the anticancer pharmacology of Tamoxifen in breast cancer cells

15. Synchrotron FTIR microspectroscopy of Escherichia coli at single-cell scale under silver-induced stress conditions

16. Zeta potential of anoxygenic phototrophic bacteria and Ca adsorption at the cell surface: possible implications for cell protection from CaCO3 precipitation in alkaline solutions

17. Ultrastructural changes in the third-stage, infective larvae of ruminant nematodes treated with sainfoin (Onobrychis viciifolia) extract

18. Endothelial estrogen receptor {alpha} plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion

19. Synchrotron FTIR microspectroscopy of the yeast Saccharomyces cerevisiae after exposure to plasma-deposited nanosilver-containing coating

20. Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism

21. Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human breast cancer cells through the modulation of cholesterol metabolism

22. Murine embryonic stem cell-derived pancreatic acinar cells recapitulate features of early pancreatic differentiation

23. Mycobacterial lipomannan induces granuloma macrophage fusion via a TLR2-dependent, ADAM9- and beta1 integrin-mediated pathway

24. Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity

25. Tamoxifen is a potent inhibitor of cholesterol esterification and prevents the formation of foam cells

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25 results on '"Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB)"'

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