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31 results on '"[ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]"'

1. Prestressed cells are prone to cytoskeleton failures under localized shear strain: an experimental demonstration on muscle precursor cells

Author

Streppa, Laura, Ratti, Francesca, Goillot, Evelyne, Devin, Anne, Schaeffer, Laurent, Arneodo, Alain, Argoul, Françoise, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire Ondes et Matière d'Aquitaine (LOMA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), ANR-10-BLAN-1516,MechaStem,Physique de la morphogenèse des plantes: propriétés dynamiques et mécaniques de la paroi des cellules du méristème(2010), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de biologie et modélisation de la cellule ( LBMC UMR 5239 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-École normale supérieure - Lyon ( ENS Lyon ), Institut de biochimie et génétique cellulaires ( IBGC ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Ondes et Matière d'Aquitaine ( LOMA ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), ANR-10-BLAN-1516,MechaStem,Physique de la morphogenèse des plantes: propriétés dynamiques et mécaniques de la paroi des cellules du méristème ( 2010 ), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Argoul, Françoise, and BLANC - Physique de la morphogenèse des plantes: propriétés dynamiques et mécaniques de la paroi des cellules du méristème - - MechaStem2010 - ANR-10-BLAN-1516 - BLANC - VALID

Subjects
[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], lcsh:Medicine, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Microscopy, Atomic Force, Cell Line, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Myoblasts, Mice, Stress, Physiological, [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [ PHYS.PHYS.PHYS-MED-PH ] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Animals, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lcsh:Science, Cell Shape, Cytoskeleton, [ PHYS.MECA.BIOM ] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], lcsh:R, [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], lcsh:Q, Stress, Mechanical
Abstract

International audience; We report on a wavelet based space-scale decomposition method for analyzing the response of living muscle precursor cells (C2C12 myoblasts and myotubes) upon sharp indentation with an AFM cantilever and quantifying their aptitude to sustain such a local shear strain. Beyond global mechanical parameters which are currently used as markers of cell contractility, we emphasize the necessity of characterizing more closely the local fluctuations of the shear relaxation modulus as they carry important clues about the mechanisms of cytoskeleton strain release. Rupture events encountered during fixed velocity shear strain are interpreted as local disruptions of the actin cytoskeleton structures, the strongest (brittle) ones being produced by the tighter and stiffer stress fibers or actin agglomerates. These local strain induced failures are important characteristics of the resilience of these cells, and their aptitude to maintain their shape via a quick recovery from local strains. This study focuses on the perinuclear region because it can be considered as a master mechanical organizing center of these muscle precursor cells. Using this wavelet-based method, we combine the global and local approaches for a comparative analysis of the mechanical parameters of normal myoblasts, myotubes and myoblasts treated with actomyosin cytoskeleton disruptive agents (ATP depletion, blebbistatin).

Published
2018
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2. Modelling Tetraselmis sp. growth-kinetics and optimizing bioactive-compound production through environmental conditions

Author

Bilel Hadrich, Imen Fendri, Chantal Pichon, Faiez Hentati, Mohamed Barkallah, Philippe Michaud, Mouna Dammak, Michel Denis, Slim Abdelkafi, Hajer Ben Hlima, Frapart, Isabelle, Unité de Biotechnologie des Algues, Biological Engineering Department, National School of Engineers of Sfax, Université de Sfax - University of Sfax, École Nationale d'Ingénieurs de Sfax | National School of Engineers of Sfax (ENIS), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Sfax, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut méditerranéen d'océanologie ( MIO ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Université de Toulon ( UTLN ) -Centre National de la Recherche Scientifique ( CNRS ), National School of Engineers of Sfax, Service des Maladies Infectieuses et Tropicales [CHU Tenon], CHU Tenon [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université

Subjects
Chlorophyll, 0106 biological sciences, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Light, Starch, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV]Life Sciences [q-bio], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 010501 environmental sciences, 01 natural sciences, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [CHIM.GENI]Chemical Sciences/Chemical engineering, Optimal culture conditions, Chlorophyta, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IDA]Life Sciences [q-bio]/Food engineering, Microalgae, [ CHIM.GENI ] Chemical Sciences/Chemical engineering, Waste Management and Disposal, Carotenoid, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, [CHIM.MATE]Chemical Sciences/Material chemistry, General Medicine, Chlorophylls, Bioactive compound, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.BBM.BP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Environmental Engineering, Bioengineering, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, 010608 biotechnology, Tetraselmis, 0105 earth and related environmental sciences, Chromatography, Renewable Energy, Sustainability and the Environment, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Carotenoids, [ CHIM.POLY ] Chemical Sciences/Polymers, Salinity, Kinetics, Light intensity, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, [ CHIM.MATE ] Chemical Sciences/Material chemistry, Gravimetric analysis, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; The aim of this study is to predict Tetraselmis cells growth-kinetic and to induce the synthesis of bioactive compounds (chlorophylls, carotenoids and starch) with high potential for biotechnological applications. Using the statistical criteria, the Baranyi-Roberts model has been selected to estimate the microalgae growth-kinetic values. The simultaneous effects of salinity, light intensity and pH of culture medium were investigated to maximize the production of total chlorophylls, carotenoids and starch. The optimal culture conditions for the production of these compounds were found using Box-Behnken Design. Results have shown that total chlorophyll and carotenoids were attained 21.6mg·g-1DW and 0.042mg·g-1DW, respectively. In addition, the highest starch content of 0.624g·g-1DW has been obtained at neutral pH with high irradiance (182μmolphotonsm-2 s-1) and low salinity (20). A highly correlation (R2 = 0.884) has been found between the gravimetric and flow cytometric measurements of chlorophyll content.

Published
2018
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3. Nanoparticules multimodales à base de lanthanides pour l’imagerie biomédicale et le suivi de cellules mésenchymateuses

Author

Santelli , Julien, Matériaux Multi-fonctionnels et Multi-échelles (CEMES-M3), Centre d'élaboration de matériaux et d'études structurales (CEMES), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-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)-Institut de Chimie du CNRS (INC)-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), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), CHROMALYS, Région Midi-Pyrénées, UPS Toulouse - Université Toulouse 3 Paul Sabatier, Marc Verelst, Robert Mauricot, Matériaux Multi-fonctionnels et Multi-échelles ( CEMES-M3 ), Centre d'élaboration de matériaux et d'études structurales ( CEMES ), Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -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 ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -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)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
nanoparticules d’oxysulfure de lanthanides, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, imagerie biomédicale multimodale, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, imagerie par résonnance magnétique, computed tomography, [CHIM.MATE]Chemical Sciences/Material chemistry, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], lanthanide oxysulfide nanoparticles, tomodensitométrie, [ CHIM.MATE ] Chemical Sciences/Material chemistry, suivi de cellules mésenchymateuses, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, magnetic resonance imaging, [ SPI.OPTI ] Engineering Sciences [physics]/Optics / Photonic, fluorescence, mesenchymal cells tracking, multimodal biomedical imaging, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging
Abstract

The objective of these works was to put into practice the use of lanthanide-based multimodal nanoparticles (NPs) for biomedical imaging in general and mesenchymal cells (MSCs) tracking in particular. To that purpose, two types of NPs have been used, both presenting a gadolinium oxysulfide (Gd2O2S) matrix allowing magnetic resonance imaging (MRI) and computed tomography. The addition of dopant elements brings fluorescence properties: europium (Gd2O2S :Eu3+) is more appropriate for an in vitro examination whereas the combination ytterbium/thulium (Gd2O2S :Yb3+/Tm3+) is more appropriate for an in vivo examination through the up-conversion process.First, we have demonstrated the possibility of visualizing those NPs over-time in a living organism with complementary methods (MRI and fluorescence). The complete study of their biodistribution and ways of elimination allowed us to highlight a hepatobiliary metabolization associated with a slow feces excretion.The labeling of a wide variety of cell types (lines and primary cells from different species) has also pointed out their potential as a universal cell tracer.Thereafter, we focused our research on mesenchymal cells tracking in a cell therapy context. Short, medium and long term biocompatibility was validated via a series of analyses (MTT, neutral red, wound healing and differentiation) and the reliability of the tracer was confirmed by detailed study of the cell labeling.Finally, after developing a custom-made system dedicated to up-conversion imaging in small animals, we were able to perform over-time tracking of those labeled cells after injection in a solid organ. We achieved multimodal imaging of the MSCs with MRI, computed tomography and up-conversion.Altogether, these results underline the potential of these nanoparticles for long term imaging in preclinical and/or clinical studies.; L’objectif de ces travaux a été de mettre en pratique l’utilisation de nanoparticules multimodales (NPs) à base de lanthanides pour l’imagerie biomédicale en général et le suivi de cellules mésenchymateuses (MSCs) en particulier. Dans cette optique, deux types de NPs ont été utilisées, présentant toutes deux une matrice d’oxysulfure de gadolinium (Gd2O2S) permettant l’imagerie par résonnance magnétique (IRM) et la tomodensitométrie. L’ajout d’éléments dopants apporte des propriétés de fluorescence : l’europium (Gd2O2S :Eu3+), plus adapté à un examen in vitro et le couple ytterbium/thulium (Gd2O2S :Yb3+/Tm3+) à un examen in vivo grâce au phénomène de conversion ascendante de photons (up-conversion).Nous avons, dans un premier temps, démontré la possibilité de visualiser ces NPs au cours du temps au sein d’un organisme vivant par des méthodes complémentaires (IRM et fluorescence). L’étude complète de leur distribution et des voies d’élimination nous a permis de mettre en évidence une métabolisation hépatobiliaire associée à une lente excrétion dans les fèces.Le marquage d’un grand nombre de types cellulaires (lignées et cellules primaires d’espèces différentes) a également mis en avant leur potentiel en tant que traceur cellulaire universel. Nous avons par la suite concentré nos travaux sur le suivi de cellules mésenchymateuses dans un contexte de thérapie cellulaire. La biocompatibilité cellulaire à court, moyen et long terme a été validée par une série d’analyses (MTT, rouge neutre, wound healing, différenciation) et la fiabilité du traceur a été confirmée par l’étude approfondie du marquage cellulaire.Enfin, après mise au point d’un système personnalisé dédié à l’imagerie par up-conversion chez le petit animal, nous avons pu réaliser le suivi de ces cellules marquées, au cours du temps après injection dans un organe solide. Nous avons alors été en mesure de visualiser les MSCs par imagerie multimodale : IRM ; tomodensitométrie et fluorescence par up-conversion.L’ensemble de ces résultats met en avant le potentiel de ces nanoparticules pour l’imagerie à long terme dans des études précliniques et/ou cliniques.

Published
2018

4. Methanol induces cytosolic calcium variations, membrane depolarization and ethylene production in arabidopsis and tobacco

Author

Rafik Errakhi, Delphine Arbelet-Bonnin, François Bouteau, Tomonori Kawano, Arnaud Lehner, Daniel Tran, Takashi Kadono, Tingting Zhao, Patrice Meimoun, Aurélien Dauphin, Hieu T H Nguyen, Laboratoire Interdisciplinaire des Energies de Demain ( LIED ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ), McGill University, Génétique et Biologie du Développement, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement ( LBD ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Kochi University of Technology ( KUT ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale ( Glyco-MEV ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire Interdisciplinaire des Energies de Demain (LIED (UMR_8236)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Biologie des Semences = Seed biology (LBD-E01), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Kochi University of Technology (KUT), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Biologie du Développement (LBD), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Arabidopsis thaliana, Aequorin, Arabidopsis, Plant Science, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 01 natural sciences, Cytosol, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Plant Growth Regulators, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cells, Cultured, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, Plant Proteins, chemistry.chemical_classification, biology, food and beverages, [ SDV.BV.PEP ] Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Depolarization, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Recombinant Proteins, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.BV.AP ] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, signalization, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, volatile, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell wall, 03 medical and health sciences, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [ SDV.BDD.GAM ] Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Tobacco, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], methanol, Reactive oxygen species, calcium, Cell Membrane, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Original Articles, Ethylenes, biology.organism_classification, Plant cell, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [ CHIM.POLY ] Chemical Sciences/Polymers, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Seedlings, Biophysics, biology.protein, Apoproteins, Reactive Oxygen Species, 010606 plant biology & botany
Abstract

BACKGROUND AND AIMS: Methanol is a volatile organic compound released from plants through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. However, molecular mechanisms that explain how methanol could affect plant defences remain poorly understood. METHODS: Using cultured cells and seedlings from Arabidopsis thaliana and tobacco BY2 expressing the apoaequorin gene, allowing quantification of cytosolic Ca(2+), a reactive oxygen species (ROS) probe (CLA, Cypridina luciferin analogue) and electrophysiological techniques, we followed early plant cell responses to exogenously supplied methanol applied as a liquid or as volatile. KEY RESULTS: Methanol induces cytosolic Ca(2+) variations that involve Ca(2+) influx through the plasma membrane and Ca(2+) release from internal stores. Our data further suggest that these Ca(2+) variations could interact with different ROS and support a signalling pathway leading to well known plant responses to pathogens such as plasma membrane depolarization through anion channel regulation and ethylene synthesis. CONCLUSIONS: Methanol is not only a by-product of PME activities, and our data suggest that [Ca(2+)](cyt) variations could participate in signalling processes induced by methanol upstream of plant defence responses.

Published
2018
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5. A 1D model of leukocyte adhesion coupling bond dynamics with blood velocity

Author

Nicolas Meunier, Bérénice Grec, Laurent Navoret, Bertrand Maury, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques d'Orsay (LM-Orsay), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Mathématiques d'Orsay ( LM-Orsay ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique Avancée ( IRMA ), and Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
0301 basic medicine, Statistics and Probability, Integrins, Support Vector Machine, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], 0206 medical engineering, Integrin, 02 engineering and technology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Stress (mechanics), 03 medical and health sciences, [ MATH.MATH-AP ] Mathematics [math]/Analysis of PDEs [math.AP], [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell Adhesion, Leukocytes, Humans, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Cell adhesion, General Immunology and Microbiology, biology, business.industry, Chemistry, Applied Mathematics, Dynamics (mechanics), Transendothelial and Transepithelial Migration, General Medicine, Structural engineering, Adhesion, Mechanics, 020601 biomedical engineering, Shear (sheet metal), Coupling (electronics), 030104 developmental biology, Drag, Modeling and Simulation, biology.protein, Endothelium, Vascular, Stress, Mechanical, General Agricultural and Biological Sciences, business, Algorithms, Blood Flow Velocity
Abstract

International audience; Cell adhesion on the vascular wall is a highly coupled process where blood flow and adhesion dynamics are closely linked. Cell dynamics in the vicinity of the vascular wall is driven mechanically by the competition between the drag force of the blood flow and the force exerted by the bonds created between the cell and the wall. Bonds exert a friction force. Here, we propose a mathematical model of such a competitive system, namely leukocytes whose capacity to create bonds with the vascular wall and transmigratory ability are coupled by integrins and chemokines. The model predicts that this coupling gives rise to a dichotomic cell dynamic, whereby cells switch from rolling to firm arrest, through non linear effects. Cells can then trans-migrate through the wall. These predicted dynamic regimes are compared to in-vitro trajectories of leukocytes. We expect that competition between friction and drag force in particle dynamics (such as shear stress-controlled nanoparticle capture) can lead to similar dichotomic mode.

Published
2018
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6. A mouse model of disseminated mantle cell lymphoma highlights a lack of activity of estrogen receptor β agonists toward tumor burden

Author

Clara Recasens-Zorzo, Gaël Roué, Brigitte Sola, Xavier Troussard, Anna Esteve-Arenys, Simon C. Body, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques ( GPMCND ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), Universitat de Barcelona ( UB ), Laboratoire d'hématologie biologique [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Vall d'Hebron University Hospital [Barcelona], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and Sola, Brigitte

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Cancer Research, Pathology, Tumor burden, Estrogen receptor, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Lymphoma, Mantle-Cell, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Mantle (mollusc), ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, Tumor Burden, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, medicine.medical_specialty, Antineoplastic Agents, Hormonal, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Animals, Estrogen Receptor beta, Humans, Estrogen receptor beta, Neoplasm Staging, business.industry, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Estrogens, medicine.disease, Xenograft Model Antitumor Assays, Lymphoma, Disease Models, Animal, 030104 developmental biology, Cell culture, Mantle cell lymphoma, Bone marrow, business
Abstract

Mantle B lymphoma (MCL) is a rare, still incurable, aggressive malignant hemopathy of mature B cells [1]. In the bone marrow and secondary lymphoid organs, tumor cells are connected with their envi...

Published
2017
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7. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in septic patients

Author

Uhel, Fabrice, Azzaoui, Imane, Grégoire, Murielle, Pangault, Céline, Dulong, Joelle, Tadié, Jean-Marc, Gacouin, Arnaud, Camus, Christophe, Cynober, Luc, Fest, Thierry, Le Tulzo, Yves, Roussel, Mikael, Tarte, Karin, Service des Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme ( PRETRRAM - EA 4466 ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Research grant from the French Intensive Care Society / Société de Réanimation de Langue Française (FICS/SRLF), Research grant from the National Institute of Cancer and Direction Générale de l'Organisation des Soins Ministère de la Santé (Projet Recherche Translationnelle 2010), Research grant from the Comité de la Recherche Translationnelle (CORECT), Rennes University Hospital, UHEL, Fabrice, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM - EA 4466), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
immune tolerance, MESH : monocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, MDSC, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, infections nosocomiales, choc septique, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], sepsis, MESH: immune tolerance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], nosocomial infections, polynucléaires neutrophiles, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : granulocytes, MESH: granulocytes, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Sepsis, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: monocytes, cytométrie en flux, flow cytometry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, granulocytes, myeloid-derived suppressor cells, cross infection, MESH: cross infection, MESH : immune tolerance, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, septic shock, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Sepsis, MESH : cross infection, monocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Rationale - Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined.Objectives - To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis.Methods - Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments.Measurements and main results - Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14HLA-DR monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14CD15 low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P Conclusions - M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

Published
2017
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8. Regulation of the ROS Response Dynamics and Organization to PDGF Motile Stimuli Revealed by Single Nanoparticle Imaging

Author

Antigoni Alexandrou, Rivo Ramodiharilafy, Cedric Bouzigues, Pierre-Louis Tharaux, Thanh-Liem Nguyen, Amy A. Claeson, Laboratoire d'optique et biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'optique et biosciences ( LOB ), École polytechnique ( X ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], medicine.medical_treatment, Clinical Biochemistry, Biochemistry, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Mice, [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cell surface receptor, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Drug Discovery, medicine, Animals, Humans, Kinase activity, Molecular Biology, Cells, Cultured, Platelet-Derived Growth Factor, Pharmacology, chemistry.chemical_classification, Reactive oxygen species, biology, Growth factor, Hydrogen Peroxide, General Medicine, Cell biology, Mice, Inbred C57BL, chemistry, Cancer cell, Second messenger system, biology.protein, Nanoparticles, Molecular Medicine, Signal transduction, Reactive Oxygen Species, Platelet-derived growth factor receptor, HeLa Cells, Signal Transduction
Abstract

International audience; Although reactive oxygen species (ROS) are better known for their harmful effects, more recently, H2O2, one of the ROS, was also found to act as a secondary messenger. However, details of spatiotemporal organization of specific signaling pathways that H2O2 is involved in are currently missing. Here, we use single nanoparticle imaging to measure the local H2O2 concentration and reveal regulation of the ROS response dynamics and organization to platelet-derived growth factor (PDGF) signaling. We demonstrate that H2O2 production is controlled by PDGFR kinase activity and EGFR transactivation, requires a persistent stimulation, and is regulated by membrane receptor diffusion. This temporal filtering is impaired in cancer cells, which may determine their pathological migration. H2O2 subcellular mapping reveals that an external PDGF gradient induces an amplification-free asymmetric H2O2 concentration profile. These results support a general model for the control of signal transduction based only on membrane receptor diffusion and second messenger degradation.

Published
2014
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9. 'Fibrous nests' in human hepatocellular carcinoma express a Wnt-induced gene signature associated with poor clinical outcome

Author

Romain Desert, Sihem Mebarki, Bruno Clément, Laurent Sulpice, Damien Bergeat, Orlando Musso, Mireille Desille, Bruno Turlin, Marie Sicard, Stéphanie Renaud, Elise Lavergne, Christine Perret, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, Université de Rennes 1, Région Bretagne, Agence Nationale de la Recherche, Institut National du Cancer, Fondation Recherche Médicale, Ligue Nationale Contre le Cancer (Comité des Côtes d’Armor), Feder, Contrat de Plan Etat Région 2007-2013 projet Cancéropôle., ANR-11-ISV1-0001,BetaCatHCC,Ciblage de la voie de signalisation Wnt/beta-caténine dans les cancers primitifs du foie(2011), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and ANR-11-ISV1-0001,BetaCatHCC,Ciblage de la voie de signalisation Wnt/beta-caténine dans les cancers primitifs du foie ( 2011 )

Subjects
Liver Cirrhosis, 0301 basic medicine, Frizzled, [SDV]Life Sciences [q-bio], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, Basement Membrane, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mesoderm, Recurrence, WNT2, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], extracellular matrix remodeling, CD44, Myofibroblasts, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], transit-amplifying liver progenitor cells, Wnt Signaling Pathway, ComputingMilieux_MISCELLANEOUS, SFRP, Liver Neoplasms, Wnt signaling pathway, LGR5, Cell Differentiation, hepatocellular carcinoma, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Gene Expression Regulation, Neoplastic, [STAT]Statistics [stat], Neoplastic Stem Cells, Stem cell, Carcinoma, Hepatocellular, [ STAT ] Statistics [stat], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, Wnt, Cancer stem cell, stem cells, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Biomarkers, Tumor, Humans, tumor microenvironment, Neoplasm Invasiveness, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Progenitor cell, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BID ] Life Sciences [q-bio]/Biodiversity, [ SDV ] Life Sciences [q-bio], [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, β-catenin, fibrogenesis, Actins, Wnt Proteins, 030104 developmental biology, Cancer research, biology.protein, Laminin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; AbstractHepatocellular carcinoma (HCC) is the 3rd cause of cancer-related death worldwide. Most cases arise in a background of chronic inflammation, extracellular matrix (ECM) remodeling, severe fibrosis and stem/progenitor cell amplification. Although HCCs are soft cellular tumors, they may contain fibrous nests within the tumor mass. Thus, the aim of this study was to explore cancer cell phenotypes in fibrous nests. Combined anatomic pathology, tissue microarray and real-time PCR analyses revealed that HCCs (n=82) containing fibrous nests were poorly differentiated, expressed Wnt pathway components and target genes, as well as markers of stem/progenitor cells, such as CD44, LGR5 and SOX9. Consistently, in severe liver fibroses (n=66) and in HCCs containing fibrous nests, weighted correlation analysis revealed a gene network including the myofibroblast marker ACTA2, the basement membrane components COL4A1 and LAMC1, the Wnt pathway members FZD1; FZD7; WNT2; LEF1; DKK1 and the Secreted Frizzled Related Proteins (SFRPs) 1; 2 and 5. Moreover, unbiased random survival forest analysis of a transcriptomic dataset of 247 HCC patients revealed high DKK1, COL4A1, SFRP1 and LAMC1 to be associated with advanced tumor staging as well as with bad overall and disease-free survival. In vitro, these genes were upregulated in liver cancer stem/progenitor cells upon Wnt-induced mesenchymal commitment and myofibroblast differentiation. In conclusion, fibrous nests express Wnt target genes, as well as markers of cancer stem cells and mesenchymal commitment. Fibrous nests embody the specific microenvironment of the cancer stem cell niche and can be detected by routine anatomic pathology analyses.

Published
2016
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10. Efferocytosis of apoptotic HPV positive cervical cancer cells by human primary fibroblasts

Author

Hermetet , François, Jacquin , Elise, Launay , Sophie, Gaiffe , Emilie, Hirchaud , Fabienne, Sandoz , Patrick, Prétet , Jean-Luc, Mougin , Christiane, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Abstract

International audience; Efficient clearance of dying cells is a fundamental physiological process for tissue development and homeostasis. The contribution of amateur phagocytes like fibroblasts to apoptotic cell efferocytosis has been established though the underlying mechanisms are not well understood. We recently demonstrated that horizontal DNA transfer can occur through the uptake of apoptotic HPV positive cancer cells by human primary fibroblasts (HPFs) leading to their transformation. In the present study, by using in vitro co-culture approaches, we confirm the role of HPFs as non-professional phagocytes in the context of apoptotic cervical cancer cell removal. Confocal microscopy imaging and flow cytometry analyses revealed that HPFs engulf more efficiently late apoptotic cells than early apoptotic targets, but their phagocytic ability remains limited compared to professional phagocytes as human monocytes-derived macrophages. Efferocytosis by HPFs occurs in a time-temperature- and calcium-dependent manner. Remodeling of actin-fibers contributes to the biogenesis of macroendocytic vacuoles. Both morphological analyses and pharmacological approaches confirmed the involvement of actin driven-phagocytosis and likely -macropinocytosis in apoptotic target internalization by HPFs. The uptake of apoptotic cell requires phosphatidylserine recognition. In HPFs, immunofluorescence and functional experiments using specific RNA interference assay suggested that this recognition is mainly mediated by Brain-specific Angiogenesis Inhibitor-1 (BAI1) and that this receptor contributes to subsequent uptake orchestration. Confocal microscopy analyses with organelle-specific markers revealed that internalized apoptotic material traffics into late phagolysosomes and specific-features of Microtubule-associated protein 1 Light Chain 3 alpha (LC3)-associated phagocytosis are observed. We conclude that efferocytosis by HPFs is mediated by phagocytosis/macropinocytosis involving phosphatidylserine recognition likely by the phosphatidylserine receptor BAI1.

Published
2016
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11. Aggressive non-Hodgkin's lymphoma: Concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome

Author

Alain Monnereau, Elizabeth Fabre-Guillevin, Pierre Soubeyran, Valérie Coulon, Houchingue Eghbali, Isabelle Soubeyran, Reza Tabrizi, Hôpital Européen Georges-Pompidou ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER

Subjects
Male, [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Oncology, Cancer Research, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, International Prognostic Index, hemic and lymphatic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Aged, 80 and over, education.field_of_study, [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], biology, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Lymphoma, Non-Hodgkin, Hematology, Middle Aged, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Interleukin-10, Gene Expression Regulation, Neoplastic, Interleukin 10, Treatment Outcome, [ SCCO.COMP ] Cognitive science/Computer science, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, Interleukin 2, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, medicine.medical_specialty, Population, [SCCO.COMP]Cognitive science/Computer science, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, education, Interleukin 6, Interleukin 4, Aged, Interleukin-6, business.industry, Receptors, Interleukin-2, medicine.disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Lymphoma, Non-Hodgkin's lymphoma, [ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], Immunology, biology.protein, Interleukin-2, Interleukin-4, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, 030215 immunology
Abstract

International audience; The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.

Published
2006
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12. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy

Author

J. Bardon, B. Matot, David Briand, P. Serrani, Clément Crochemore, Miria Ricchetti, Laurent Chatre, Tarek Sharshar, Grégory Jouvion, Mathilde Latil, Pierre Rocheteau, P. G. Carlier, Miryam Mebarki, A. Lafoux, Nicola Latronico, Pier Paolo Lecci, Fabrice Chrétien, C. Huchet, Rocheteau, Pierre, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), Cellules Souches et Développement, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Résonance Magnétique Nucléaire (LRMN), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Anesthesia and Reanimation Department, Department of Surgery, University of Brescia, Unité de recherche de l'institut du thorax (ITX-lab), 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de réanimation médico-chirurgicale adulte, Hôpital Raymond Poincaré [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuropathologie, Centre Hospitalier Sainte Anne, This work was supported by Région Ile de France, Fondation pour les Gueules Cassées, Société de Réanimation de Langue Française and Agence Nationale de la Recherche (ANR 11BSV202552), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Résonance Magnétique Nucléaire ( LRMN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service MIRCEN ( MIRCEN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Hopital Raymond Poincaré, Garches, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), and Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
Male, Genetics and Molecular Biology (all), medicine.medical_treatment, General Physics and Astronomy, stem-cell, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Biochemistry, Transgenic, sepsis, Mice, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cells, Cultured, 2. Zero hunger, satellite cells, Cultured, Multidisciplinary, Stem Cells, Chemistry (all), Mitochondria, 3. Good health, Cytokine, medicine.anatomical_structure, Cytokines, Muscle, Stem cell, medicine.symptom, Satellite Cells, Skeletal Muscle, Skeletal Muscle, Cells, Mice, Transgenic, Peritonitis, Biology, Mesenchymal Stem Cell Transplantation, Article, General Biochemistry, Genetics and Molecular Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Sepsis, Physics and Astronomy (all), Intensive care, medicine, Animals, Regeneration, mesenchymal stem cells, Mesenchymal stem cell, Muscle weakness, Skeletal muscle, Gene Expression Regulation, Mitochondria, Muscle, Reactive Oxygen Species, Biochemistry, Genetics and Molecular Biology (all), General Chemistry, medicine.disease, infection, Systemic inflammatory response syndrome, Immunology
Abstract

Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity., Sepsis patients often develop muscle atrophy that can last for years. Here the authors show in a mouse model that sepsis causes long-term impairment of the satellite cells, affecting mitochondrial function and energy metabolism, and that injection of mesenchymal stem cells restores satellite cell metabolism and muscle regeneration.

Published
2015
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13. Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort

Author

Nathalie Martins, Peggy Sirvain-Trukniewicz, Margaret L. Rand, Marc Trossaert, Jenny Goudemand, Paquita Nurden, Mathieu Fiore, Schéhérazade Benabdallah‐Guerida, Roseline d Oiron, Pierre Sié, Marie-Christine Alessi, Juan Pablo Fronthroth, Mathias Canault, Lorenzo Alberio, Christine Vinciguerra, Mathilde Fretigny, Diane J. Nugent, Mariana Bonduel, Alan T. Nurden, Claude Negrier, Véronique Latger-Cannard, Xavier Pillois, Arnaud Couloux, Yves Gruel, Roland Heilig, Marie Dreyfus, Gironde, Institute of Electronics, Computer and Telecommunication Engineering (IEIIT-CNR), Politecnico di Torino [Torino] (Polito)-Consiglio Nazionale delle Ricerche [Torino] (CNR), Clinatec - Centre de recherche biomédicale Edmond J.Safra, Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d'hématologie - Hémostase, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Francois Rabelais [Tours], Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hémostase, Inflammation et sepsis (EA 4609), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Atomic Energy Agency (AEA), Atomic Energy Agency, Department of Haematology and Central Haematology Laboratory, University Hospital Inselspital, Universite Federale du Ceara (UFC), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Politecnico di Torino = Polytechnic of Turin (Polito)-Consiglio Nazionale delle Ricerche [Torino] (CNR), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Universidade Federal do Ceará = Federal University of Ceará (UFC), CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, IEIIT-CNR, Politecnico di Torino [Torino] ( Polito ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre Hospitalier Universitaire [Grenoble] ( CHU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), UMR 6239, Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hémostase, Inflammation et sepsis, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-VetAgro Sup ( VAS ), Atomic Energy Agency ( AEA ), Universite Federale du Ceara ( UFC ), Centre National de Séquençage (Genoscope) ( CNS ), Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ), CNR Institute of Electronics, Computer and Telecommunication Engineering [Torino] (CNR | IEIIT), CNR Istituto di elettronica e di ingegneria dell'informazione e delle telecomunicazioni (CNR | IEIIT), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)-National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Models, Molecular, Genotype, Protein Conformation, RNA Splicing, DNA Mutational Analysis, Integrin alpha2, 610 Medicine & health, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Platelet Glycoprotein GPIIb-IIIa Complex, Biology, medicine.disease_cause, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cohort Studies, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Genetics, medicine, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Humans, Missense mutation, Coding region, Protein Interaction Domains and Motifs, Genetic Testing, Gene, ComputingMilieux_MISCELLANEOUS, Genetic Association Studies, Genetics (clinical), Sequence Deletion, Gene Rearrangement, Mutation, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Integrin beta3, Intron, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Exons, Molecular biology, Stop codon, Exon skipping, Phenotype, RNA splicing, RNA Splice Sites, Thrombasthenia
Abstract

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in 7 unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits thereby interfering with integrin maturation and/or function. Our study extends knowledge of Glanzmann thrombasthenia and the pathophysiology of an integrin. This article is protected by copyright. All rights reserved.

Published
2015
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14. The cell wall pectic polymer rhamnogalacturonan-II is required for proper pollen tube elongation: implications of a putative sialyltransferase-like protein

Author

Arnaud Lehner, Marie Christine Kiefer-Meyer, Marie Dumont, Jean-Claude Mollet, Sophie Bouton, Patrice Lerouge, Aline Voxeur, Jérôme Pelloux, Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-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 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 Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, University of Rouen, 'Trans Channel Wallnet' project, ERDF, Biologie des Plantes et Innovation (BIOPI), Université de Picardie Jules Verne (UPJV), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale ( Glyco-MEV ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut Jean-Pierre Bourgin ( IJPB ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, 0977 Unité associée de Biologie forestière, and Institut National de la Recherche Agronomique ( INRA )

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Arabidopsis thaliana, Polymers, [SDV]Life Sciences [q-bio], Mutant, Arabidopsis, MESH : Pollen Tube, Kdo, Plant Science, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, MESH : Arabidopsis Proteins, MESH : Arabidopsis, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell Wall, Gene Expression Regulation, Plant, Genes, Reporter, MESH : Pectins, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], plant cell wall, [SDV.BDD]Life Sciences [q-bio]/Development Biology, RG-II, food and beverages, MESH : Sialyltransferases, [ SDV.BV.PEP ] Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Articles, MESH : Genes, Reporter, Dha, MESH : Phenotype, [ SDV.BV.AP ] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Phenotype, Biochemistry, Germination, Organ Specificity, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pectins, Pollen, Pollen tube, MESH : Mutation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell wall, MESH : Organ Specificity, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [ SDV.BDD.GAM ] Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH : Pollen, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH : Polymers, MESH : Cell Wall, Reporter gene, Arabidopsis Proteins, MESH : Sugar Acids, pectin motif, Wild type, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], sialyltransferase-like protein, Sugar Acids, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Molecular biology, pollen tube, Sialyltransferases, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [ CHIM.POLY ] Chemical Sciences/Polymers, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Rhamnogalacturonan-II, Mutation, MESH : Gene Expression Regulation, Plant
Abstract

International audience; BACKGROUND AND AIMSRhamnogalacturonan-II (RG-II) is one of the pectin motifs found in the cell wall of all land plants. It contains sugars such as 2-keto-3-deoxy-d-lyxo-heptulosaric acid (Dha) and 2-keto-3-deoxy-d-manno-octulosonic acid (Kdo), and within the wall RG-II is mostly found as a dimer via a borate diester cross-link. To date, little is known regarding the biosynthesis of this motif. Here, after a brief review of our current knowledge on RG-II structure, biosynthesis and function in plants, this study explores the implications of the presence of a Golgi-localized sialyltransferase-like 2 (SIA2) protein that is possibly involved in the transfer of Dha or Kdo in the RG-II of Arabidopsis thaliana pollen tubes, a fast-growing cell type used as a model for the study of cell elongation.METHODS:Two heterozygous mutant lines of arabidopsis (sia2-1+/- and qrt1 × sia2-2+/-) were investigated. sia2-2+/- was in a quartet1 background and the inserted T-DNA contained the reporter gene β-glucuronidase (GUS) under the pollen-specific promoter LAT52. Pollen germination and pollen tube phenotype and growth were analysed both in vitro and in vivo by microscopy.KEY RESULTS:Self-pollination of heterozygous lines produced no homozygous plants in the progeny, which may suggest that the mutation could be lethal. Heterozygous mutants displayed a much lower germination rate overall and exhibited a substantial delay in germination (20 h of delay to reach 30 % of pollen grain germination compared with the wild type). In both lines, mutant pollen grains that were able to produce a tube had tubes that were either bursting, abnormal (swollen or dichotomous branching tip) or much shorter compared with wild-type pollen tubes. In vivo, mutant pollen tubes were restricted to the style, whereas the wild-type pollen tubes were detected at the base of the ovary..CONCLUSIONS:This study highlights that the mutation in arabidopsis SIA2 encoding a sialyltransferase-like protein that may transfer Dha or Kdo on the RG-II motif has a dramatic effect on the stability of the pollen tube cell wall.

Published
2014
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15. Interactions between sub-10 nm iron and cerium oxide nanoparticles and 3T3 fibroblasts : the role of the coating and aggregation state

Author

Malak Safi, Olivier Sandre, Jean-François Berret, Nathalie Mignet, Hiba Sarrouj, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Team 3 LCPO : Polymer Self-Assembly & Life Sciences, Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), TEAM 3 LCPO, Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), THEME 2, Laboratoire de Chimie des polymères organiques ( LCPO ), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ) -Physicochimie des Electrolytes, Colloïdes et Sciences Analytiques ( PECSA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Unité de Pharmacologie Chimique et Génétique ( UPCG - UMR_S 640/UMR 8151 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
Cerium oxide, Time Factors, Light, Iron oxide, Metal Nanoparticles, Nanoparticle, Cell Count, Centrifugation, 02 engineering and technology, Ferric Compounds, 01 natural sciences, Nanomaterials, Mice, chemistry.chemical_compound, Coated Materials, Biocompatible, Coating, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Scattering, Radiation, General Materials Science, Cell Aggregation, Condensed Matter - Materials Science, Cerium, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 3. Good health, Membrane, Mechanics of Materials, 0210 nano-technology, Subcellular Fractions, Materials science, Cell Survival, chemistry.chemical_element, FOS: Physical sciences, Bioengineering, engineering.material, 010402 general chemistry, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Animals, Particle Size, Electrical and Electronic Engineering, Mechanical Engineering, Materials Science (cond-mat.mtrl-sci), General Chemistry, Fibroblasts, Culture Media, 0104 chemical sciences, Molecular Weight, chemistry, Nanotoxicology, [ CHIM.MATE ] Chemical Sciences/Material chemistry, NIH 3T3 Cells, engineering, Biophysics
Abstract

Recent nanotoxicity studies revealed that the physico-chemical characteristics of engineered nanomaterials play an important role in the interactions with living cells. Here, we report on the toxicity and uptake of the cerium and iron oxide sub-10 nm nanoparticles by NIH/3T3 mouse fibroblasts. Coating strategies include low-molecular weight ligands (citric acid) and polymers (poly(acrylic acid), MW = 2000 g mol-1). Electrostatically adsorbed on the surfaces, the organic moieties provide a negatively charged coating in physiological conditions. We find that most particles were biocompatible, as exposed cells remained 100% viable relative to controls. Only the bare and the citrate-coated nanoceria exhibit a slight decrease of the mitochondrial activity for cerium concentrations above 5 mM (equivalent to 0.8 g L-1). We also observe that the citrate-coated particles are internalized by the cells in large amounts, typically 250 pg per cell after a 24 h incubation for iron oxide. In contrast, the polymer-coated particles are taken up at much lower rates (< 30 pg per cell). The strong uptake shown by the citrate-coated particles is related to the destabilization of the dispersions in the cell culture medium and their sedimentation down to the cell membranes. In conclusion, we show that the uptake of nanomaterials by living cells depends on the coating of the particles and on its ability to preserve the colloidal nature of the dispersions., 9 figures, 2 tables

Published
2010
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16. Breaking the VE-cadherin bonds

Author

Julie Gavard, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gavard, Julie, Institut Cochin ( UMR_S567 / UMR 8104 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Cell Membrane Permeability, Endothelium, Angiogenesis, Biophysics, Vascular permeability, Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Biochemistry, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Structural Biology, Antigens, CD, Cell Behavior (q-bio.CB), [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Genetics, medicine, Cell Adhesion, Compartment (development), Humans, Cell adhesion, Cytoskeleton, Molecular Biology, Tight junctions, Tight junction, Cell Biology, Cadherins, VEGF, Cell biology, medicine.anatomical_structure, Intercellular Junctions, FOS: Biological sciences, Adhesion, Quantitative Biology - Cell Behavior, Endothelium, Vascular, VE-cadherin
Abstract

International audience; Exchanges between the blood compartment and the surrounding tissues require a tight regulation by the endothelial barrier. Recent reports inferred that VE-cadherin, an endothelial specific cell-cell adhesion molecule, plays a pivotal role in the formation, maturation and remodeling of the vascular wall. Indeed, a growing number of permeability inducing factors (PIFs) was shown to elicit signaling mechanisms culminating in VE-cadherin destabilization and global alteration of the junctional architecture. Conversely, anti-PIFs protect from VE-cadherin disruption and enhance cell cohesion. These findings provide evidence on how endothelial cell-cell junctions impact the vascular network, and change our perception about normal and aberrant angiogenesis.

Published
2008
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17. Design and synthesis of intrinsically cell-penetrating nucleopeptides

Author

Piero Geotti-Bianchini, Fernando Formaggio, Alberto Bianco, Olivier Chaloin, Julien Beyrath, Immunologie et chimie thérapeutiques ( ICT ), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, and Universita degli Studi di Padova

Subjects
peptide nucleic acids, PNA, helical peptides, Molecular recognition, Cells, Cell, Molecular Sequence Data, Biochemistry, Nucleobase, Cell Line, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, medicine, Side chain, Cytotoxic T cell, Humans, Amino Acid Sequence, Physical and Theoretical Chemistry, Peptide sequence, Chemistry, Organic Chemistry, medicine.anatomical_structure, Pyrimidines, Cell culture, Purines, Drug Design, Biophysics, Peptides, Nucleus
Abstract

International audience; Nucleopeptides, which are constituted of alpha-amino acids bearing nucleobases at their side chains, are able to penetrate into cells and to reach the nucleus without cytotoxic effects.

Published
2008
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18. Confocal analysis of hedgehog morphogenetic gradient coupled with fluorescent in situ hybridization of hedgehog target genes

Author

Gallet, Armel, Thérond, Pascal P, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
Embryo, Nonmammalian, Microscopy, Confocal, Staining and Labeling, Genes, Insect, RNA Probes, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Drosophila melanogaster, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Image Processing, Computer-Assisted, Morphogenesis, Animals, Hedgehog Proteins, RNA, Antisense, Digoxigenin, In Situ Hybridization, Fluorescence
Abstract

Hedgehog (Hh) family members are secreted proteins that can act at short and long range to direct cell fate decisions during developmental processes. In both Drosophila and vertebrates, the morphogenetic gradient of Hh must be tightly regulated for correct patterning. The posttranslational modification of Hh by a cholesterol adduct participates in such regulation. We have shown that cholesterol modification is necessary for the controlled long-range activity of Drosophila Hh, as observed for its vertebrate counterpart Sonic Hh. The presence of cholesterol on Hh allows the observation of large apical punctuate structures of Hh (Hh-LPSs) at a distance from the Hh source both in embryos and in imaginal discs. The Hh-LPSs apical distribution reflects the Hh gradient and is temporally regulated. Hh gradient modulation is directly related to the dynamic expression of the Hh target gene serrate (ser), shown by immunofluorescent detection of Hh coupled with fluorescent in situ hybridization of ser.

Published
2007

19. Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts

Author

Xavier Decrouy, Jean-François Renaud, Catherine Rucker-Martin, Dominique Segretain, Claude Delcayre, Sisareuth Tan, Stéphane N. Hatem, Irene Dunia, Paul Milliez, Roger Vranckx, Michel Recouvreur, Remodelage tissulaire et fonctionnel : signalisation et physio-pathologie (RTFSPP), Université Paris-Sud - Paris 11 (UP11)-Centre chirurgical Marie Lannelongue-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Cardiovasculaire de Lariboisiere, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Mécanismes, pathogénies et thérapeutiques expérimentales de remodelage, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, génétique et pharmacologie du remodelage cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France, Fondation pour la Recherche Médicale, Société Française de Cardiologie, ANR-05-PCOD-006-01, Université Paris-Sud - Paris 11 (UP11)-Centre Chirurgical Marie Lannelongue (CCML)-Centre National de la Recherche Scientifique (CNRS), Remodelage tissulaire et fonctionnel : signalisation et physio-pathologie ( RTFSPP ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre chirurgical Marie Lannelongue-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
medicine.medical_specialty, Physiology, Gap junction, Immunoblotting, Myocardial Infarction, Connexin, Cell Communication, 030204 cardiovascular system & hematology, Connexon, Connexins, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, chemistry.chemical_compound, Imaging, Three-Dimensional, 0302 clinical medicine, Physiology (medical), Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Freeze Fracturing, Humans, Myocyte, Heart Atria, 030304 developmental biology, 0303 health sciences, Lucifer yellow, Atrium (architecture), business.industry, Gap Junctions, Atrial fibrillation, medicine.disease, Immunohistochemistry, Fibrosis, Rats, Microscopy, Electron, medicine.anatomical_structure, chemistry, Connexin 43, Cardiology, Biophysics, cardiovascular system, Atrial myocardium, sense organs, Cardiology and Cardiovascular Medicine, Intercalated disc, business
Abstract

International audience; OBJECTIVES: The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels. METHODS: Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer. RESULTS: In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization. CONCLUSION: Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.

Published
2006
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20. Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation

Author

Blons , Hélène, Côté , Jean-François, Le Corre , Delphine, Riquet , Marc, Fabre-Guillevin , Elizabeth, Laurent-Puig , Pierre, Danel , Claire, CHU Trousseau [APHP], Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Bases moléculaires de la réponse aux xénobiotiques ( U775 (IFR95) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), and Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [ SCCO.COMP ] Cognitive science/Computer science, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Abstract

International audience; In lung cancer, an association was made between drastic clinical response to epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic mutations within the tyrosine kinase domain of the EGFR. In some cases, patients with partial response or disease stabilization do not always have EGFR-mutated tumors. To go further in the characterization of the EGF pathway, we screened EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers from men). Associations between TP53 mutations, clinicopathologic parameters, and EGF pathway molecular alterations were analyzed. All mutations were exclusive and essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were linked to female sex, absence of smoking, late age at diagnosis, and adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in invasive ADC with BAC component, microdissection assays showed that mutations were retrieved in both tumor subtypes suggesting that EGFR mutations appear early in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking, younger age at diagnosis, and ADC subtype regardless of BAC differentiation. These results suggest the existence of distinct carcinogenesis pathways both leading to disruption of EGF regulation and targeted either by tobacco carcinogens or by unidentified toxic. The identification of BAC features in ADC helps clustering patients that are more likely to fit the EGFR-mutated group.

Published
2006

21. Prostate-specific antigen doubling-time (PSA DT) before onset of chemotherapy as survival predictor for hormone refractory prostate cancer (HRPC) patients

Author

Stéphane Oudard, E. Fontaine, A. Banu, Arnaud Mejean, Jacques Medioni, Jean-Marie Andrieu, Eugeniu Banu, E. Fabre Guillevin, Nicolas Thiounn, Florian Scotté, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NEANT, neant, Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales ( UPD5 Sciences ), and Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Oncology, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, Cancer Research, medicine.medical_specialty, Prognostic factor, medicine.medical_treatment, 030232 urology & nephrology, [SCCO.COMP]Cognitive science/Computer science, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Doubling time, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Gynecology, Chemotherapy, [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], business.industry, Prostatectomy, medicine.disease, Hormone refractory prostate cancer, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 3. Good health, [ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], Prostate-specific antigen, [ SCCO.COMP ] Cognitive science/Computer science, 030220 oncology & carcinogenesis, Hormonal therapy, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract

International audience; Background: PSA DT has been reported as a prognostic factor in prostate cancer patients (pts) who relapse after radical prostatectomy, radiation or hormonal therapy. The rate at which the PSA is rising is known to correlate with cancer aggressiveness. We evaluated the interest of the initial PSA DT value, before start of chemotherapy (CT), as a surrogate end point for survival of metastatic HRPC pts. Methods: PSA DT was calculated as log x 2 divided by the slope of the log PSA line (the difference in the 2 log PSA values divided by the time between). A minimum of three PSA measurements were required, maximum three months before start of CT. The primary outcome measure was overall survival. Differences in survival rates and PSA DT were calculated using the log-rank and Cox hazard regression methods, stratified according to CT regimen. All statistical tests were two-sided. Hazard ratio (HR) and relative risk reduction were also estimated with 95% confidence interval (CI). Results: A retrospective analysis was performed on 202 metastatic HRPC pts, registered from June 1999 to July 2004 in a single institution. Pts received as first-line CT: docetaxel- (77%) or mitoxantrone (23%) based regimen. The median PSA DT value was 44 days (range 5-1028 days) and median interval between two consecutive PSA determinations before CT (used tu estimate the PSA DT) was 21 days. Overall, there were 124 deaths (61%). Median survival was 14.3 months (95% CI, 10.5 to 18 months) for pts with PSA DT < 44 days vs 25.6 months (95% CI, 16.3 to 34.9 months) for pts with PSA DT > 44 days. There were significant differences between survival distributions of PSA DT categories (log-rank, p=0.006), independently of CT regimen. The stratified HR was 0.61 (95% CI, 0.43 to 0.87) with a relative risk reduction of 39% (95% CI, 13% to 57%). Conclusions: A low PSA DT before onset of CT in HRPC pts was associated with an increased risk of death. This parameter could be a potential auxiliary end point in the evaluation of new cytotoxic drugs in metastatic HRPC setting. These data may be also useful in the design of clinical trials and the identification of men for enrolment into experimental protocols.

Published
2005
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22. Docetaxel versus mitoxantrone as first-line chemotherapy for hormone-refractory prostate cancer (HRPC) patients. A meta-analysis of 3-year overall survival results. Journal of Clinical Oncology

Author

Oudard , Stéphane, Banu , Eugeniu, Banu , Adela, Scotté , Florient, Levy , Eric, Medioni , Jacques, Fabre-Guillevin , Elizabeth, Ayllon , Jorge, Arakelyan , Nina, Andrieu , Jean-Marie, Davesne, Frédéric, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales ( UPD5 Sciences ), and Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SCCO.COMP]Cognitive science/Computer science, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SCCO.COMP] Cognitive science/Computer science, [ SCCO.COMP ] Cognitive science/Computer science, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [INFO.INFO-GT] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract

International audience; Background: Docetaxel (DTX) based chemotherapy is considered the standard treatment for metastatic HRPC patients (pts), with a median survival advantage of 2 months, compared to mitoxantrone (MT). DTX advantage at long term is not defined and further evaluations are needed. Methods: We conducted a meta-analysis to assess the effect of DTX chemotherapy (CT) on overall survival (OS) compared to MT for metastatic HRPC pts. OS probabilities at 12, 18, 24, 30 and 36 months, were considered as the endpoints of interest. Subgroups analysis were performed to evaluate the impact on OS of DTX dose intensity (DI), between dose-dense (q1w) and dose-intense (q3w) schedules. Estimates of the effectiveness of CT were expressed as relative risk reduction (RRR), using a fixed effects model. Associated statistics with 95% confidence interval (CI) were calculated based on adjusted number of pts at risk and events (according to the extent of follow-up) using EasyMA software. Results: Three randomized controlled trials comparing DTX with MT-based CT in HRPC pts were selected (Tannock, Petrylak, NEJM 2004; Oudard, JCO 2005). A total of 1807 pts were included, 1092 allocated to DTX and 715 allocated to MT. The follow-up range was 13.9-58.5 months. No differences were found according to Gleason score, performance status and sites of metastasis. Overall analysis demonstrates a significant OS benefit for DTX at any time points, without any significant heterogeneity (Table). There was a significant difference in OS in favor of DTX dose-intense arm comparing to MT, with no OS benefit for DTX dose-dense schedule. The rank test for publication bias were not significant. Conclusions: This meta-analysis shows on a large data set that DTX-based CT significantly reduced the risk of death by 8-21%, a benefit persisting 3 years later after the start of CT. The benefit of DTX over MT was related to DTX schedule and dose-intense model.

Published
2005

23. Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and cutaneous toxicity of the hand

Author

Jean-Marc Tourani, Florian Scotté, Michel Peyromaure, Eric Levy, Stéphane Oudard, Elisabeth Fabre-Guillevin, Emmanuelle Magherini, S. Marsan, Eugeniu Banu, Jean-Marie Andrieu, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), CHU Necker - Enfants Malades [AP-HP], Laboratoires Sanofi-Aventis, Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales ( UPD5 Sciences ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cancer Research, Docetaxel, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030207 dermatology & venereal diseases, 0302 clinical medicine, Freezing, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], integumentary system, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Combination chemotherapy, Middle Aged, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Oncology, 030220 oncology & carcinogenesis, [ SCCO.COMP ] Cognitive science/Computer science, Toxicity, Adult Aged Antineoplastic Agents, Female, Taxoids, medicine.drug, Adult, medicine.medical_specialty, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, Protective Humans Male Middle Aged Nail Diseases/chemically induced/*prevention & control Skin Diseases/chemically induced/*prevention & control Taxoids/*adverse effects, [SCCO.COMP]Cognitive science/Computer science, Skin Diseases, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Nail Diseases, 03 medical and health sciences, Phytogenic/*adverse effects Case-Control Studies Female Freezing *Gloves, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, Aged, business.industry, Onycholysis, Cancer, medicine.disease, Antineoplastic Agents, Phytogenic, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Surgery, Clinical trial, [ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], Multicenter study, Nail disease, Case-Control Studies, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Gloves, Protective, business
Abstract

Purpose Onycholysis and skin toxicity occur in approximately 30% of patients treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of docetaxel-induced onycholysis and skin toxicity. Patients and Methods Patients receiving docetaxel 75 mg/m2 alone or in combination chemotherapy were eligible for this case-control study. Each patient wore an FG for a total of 90 minutes on the right hand. The left hand was not protected and acted as the control. Onycholysis and skin toxicity were assessed at each cycle by National Cancer Institute Common Toxicity Criteria and documented by photography. Wilcoxon matched-pairs rank test was used. Results Between August 2002 and September 2003, 45 patients were evaluated. Onycholysis and skin toxicity were significantly lower in the FG-protected hand compared with the control hand (P = .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73% v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between the FG-protected and the control hand, respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity). Five patients (11%) experienced discomfort due to cold intolerance. Conclusion FG significantly reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management to improve a patient's quality of life.

Published
2005
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24. Optimum timing of Gefinitib therapy in metatastic non-small cell lung cancer (NSCLC) patients

Author

Ayllon, Jorge, Plazanet, Vincent, Fabre-Guillevin, Elizabeth, Banu, Eugeniu, Bonan, Brigitte, Oudard, Stéphane, Le Pimpec-Barthes, Françoise, Théou, Nathalie, Sors, Hervé, Andrieu, Jean-Marie, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), SANOFI AVENTIS, SANOFI Recherche, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales ( UPD5 Sciences ), Université Paris Descartes - Paris 5 ( UPD5 ), Davesne, Frédéric, and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SCCO.COMP]Cognitive science/Computer science, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ INFO.INFO-GT ] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SCCO.COMP] Cognitive science/Computer science, [ SCCO.COMP ] Cognitive science/Computer science, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [INFO.INFO-GT] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], neoplasms, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract

International audience; Background: Gefitinib (IressaTM) is approved in for use as monotherapy for the treatment of patients (pts) with locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel chemotherapy (CT). CT that include a taxane, vinorelbine or gemcitabine remains the alternative for the second- and third-line CT. The modality of combining these CT in a sequential manner and the place of target therapies could have a major impact on survival. Methods: The present analysis evaluates the efficacy of Gefitinib for metastatic NSCLC pts. The primary outcome measure was the impact of the moment of gefitinib initiation on Time from Primary Diagnosis (TPD). TPD was calculated from primary diagnosis until death or last follow-up. Cox hazard regression analysis was performed, stratified according the initial stage of disease (AJCC 1997) and baseline ECOG performance status (PS). Progression-free survival (PFS), overall survival (OS) and TPD were estimated by Kaplan-Meier method. Gefitinib was given at a dose of 250 mg daily until disease progression in an expanded access program. Results: A retrospective analysis was performed on 71 pts, treated with gefitinib from August 2001 to October 2004 in a single institution. Median age was 59 year (range 44-85), sex M/F: 52/19 pts, ECOG PS: 0-1/2-3: 20/44 pts. Pts distribution according to treatment line was:17 pts (24%) receiving gefitinib as second-line, 16 pts (23%) as third-line, 23 pts (32%) as fourth-line CT. There were 4 pts (6%) with partial response, and 15 pts (21%) with stable disease. The median PFS and OS were 2.6 months (95% CI,1.8-3.4 months) and 5 months (95% CI,3-7 months), respectively, independently of CT line number. The median TPD for our cohort was 18.5 months (95% CI, 15.7-21.2 months). A negative and strong association (Cox coefficient = -0.6) between TPD and the moment of gefitinib initiation was observed (P=0.006, two-sided), demonstrating a major impact of precocity of treatment initiation. Conclusions: Our analysis demonstrates that the prognosis in these patients depends on the precocity of gefitinib initiation. These data may be useful in the design of clinical trials to earlier introduce target therapy, combined with chemotherapy.

Published
2005

25. Catalase activity and expression in developing sunflower seeds as related to drying

Author

Françoise Corbineau, Juliette Leymarie, Arnaud Lehner, Daniel Côme, Sandra Rousseau, Christophe Bailly, Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biologie des Semences = Seed biology (LBD-E01), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Laboratoire de Biologie du Développement ( LBD ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie des Semences = Seed biology ( LBD-E01 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale ( Glyco-MEV ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), VIBS ( GIPSA-VIBS ), Département Images et Signal ( GIPSA-DIS ), Grenoble Images Parole Signal Automatique ( GIPSA-lab ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Grenoble Images Parole Signal Automatique ( GIPSA-lab ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS)

Subjects
0106 biological sciences, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Physiology, MESH : Protein Subunits, Plant Science, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 01 natural sciences, Lipid peroxidation, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Gene Expression Regulation, Plant, Malondialdehyde, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, 2. Zero hunger, MESH : Isoenzymes, 0303 health sciences, MESH: Helianthus, [ SDV.BV.PEP ] Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, food and beverages, Helianthus annuus, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Catalase, MESH: Protein Subunits, Sunflower, Isoenzymes, Horticulture, [ SDV.BV.AP ] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, seed drying, Germination, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Seeds, MESH: Isoenzymes, Helianthus, MESH: Hydrogen Peroxide, seed development, Peroxidase, MESH: Malondialdehyde, hydrogen peroxide, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Flowers, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 03 medical and health sciences, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [ SDV.BDD.GAM ] Life Sciences [q-bio]/Development Biology/Gametogenesis, MESH : Catalase, MESH: Catalase, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Botany, MESH : Helianthus, MESH: Gene Expression Regulation, Plant, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, MESH : Malondialdehyde, MESH : Flowers, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Flowers, MESH : Seeds, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [ CHIM.POLY ] Chemical Sciences/Polymers, Protein Subunits, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, MESH: Seeds, biology.protein, Dormancy, MESH : Hydrogen Peroxide, Desiccation, MESH : Gene Expression Regulation, Plant, 010606 plant biology & botany
Abstract

International audience; Changes in catalase (CAT) activity and in CAT isoform pattern and expression were investigated in developing sunflower (Helianthus annuus L.) seeds during desiccation on the mother plant and after artificial drying on the flowerheads. Seeds regularly desiccated during their development on the mother plant and reached mass maturity at c. 42 d after flowering (DAF). Freshly harvested seeds did not germinate at any stage of development because they were dormant, but their dormancy was broken after 5-6 months of dry storage. Immature seeds were desiccation-tolerant at 24 DAF since they were able to germinate fully after artificial drying on the flowerheads followed by dry storage. CAT activity increased in non-dehydrated seeds during their development, reaching a maximum a little after seed mass maturity and after artificial drying in immature seeds. This stimulation of CAT activity by natural and artificial drying was related to changes in CAT isoform pattern. Of the four constitutive CAT subunits, that of 59 kDa was always present, but dehydration induced the synthesis of a 55 kDa subunit. This synthesis of the CAT 55 kDa subunit resulted from an activation of the CATA1 gene, suggesting that the regulation of catalase activity and synthesis by drying occurred at the transcriptional level. The increase in CAT activity induced by seed drying was associated with a decrease in hydrogen peroxide level and in lipid peroxidation. These results suggest that CAT plays a role during seed desiccation by preventing dehydration-related oxidative damage and that H(2)O(2) may play a role in the regulation of CAT gene expression and the transduction pathway of the dehydration signal.

Published
2004
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26. AMP-activated protein kinase and hepatic genes involved in glucose metabolism

Author

Dalila Azzout-Marniche, Pascal Ferré, Fabienne Foufelle, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Azzout-Marniche, Dalila

Subjects
MESH : RNA, Messenger, Transcription, Genetic, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], AMP-Activated Protein Kinases, Mitogen-activated protein kinase kinase, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Multienzyme Complexes, Biochemistry, MAP2K7, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ASK1, MESH: Animals, MESH: AMP-Activated Protein Kinases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Gene Expression Regulation, Enzymologic, MESH : AMP-Activated Protein Kinases, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH : Multienzyme Complexes, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glucose, Liver, 030220 oncology & carcinogenesis, MESH : Protein-Serine-Threonine Kinases, MESH: Enzyme Activation, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein Serine-Threonine Kinases, Biology, Gene Expression Regulation, Enzymologic, MESH: Protein-Serine-Threonine Kinases, MESH : Gene Expression Regulation, Enzymologic, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], 03 medical and health sciences, Multienzyme Complexes, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, RNA, Messenger, c-Raf, Protein kinase A, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, MESH : Glucose, MESH: Transcription, Genetic, MESH : Humans, Cyclin-dependent kinase 2, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Liver, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein kinase R, Enzyme Activation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Glucose, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], biology.protein, Cyclin-dependent kinase 9, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Liver
Abstract

International audience; Mammalian AMP-activated protein kinase presents strong structural and functional similarities with the yeast sucrose non-fermenting 1 (Snf1) kinase involved in the derepression of glucose-repressed genes. It is now clearly established that AMP-activated protein kinase in the liver decreases glycolytic/lipogenic gene expression as well as genes involved in hepatic glucose production. This is achieved through a decreased transcriptional efficiency of transcription factors such as sterol-regulatory-element-binding protein-1c, carbohydrate-response-element-binding protein, hepatocyte nuclear factor 4 alpha or forkhead-related protein. Clearly, the long-term consequences of AMP-activated protein kinase activation have to be taken into account if activators of this enzyme are to be designed as anti-diabetic drugs.

Published
2003
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27. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice

Author

Isabelle Hainault, Dalila Azzout-Marniche, Pascal Ferré, Lydia Bertry-Coussot, Dominique Bécard, Fabienne Foufelle, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Azzout-Marniche, Dalila, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)

Subjects
Male, MESH : RNA, Messenger, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: CCAAT-Enhancer-Binding Proteins, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, Homeostasis, Insulin, Glucose homeostasis, MESH: Animals, 0303 health sciences, MESH: Mice, Inbred CBA, Glycogen, Gene Transfer Techniques, MESH: Adenoviridae, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Genetic Vectors, 3. Good health, MESH : DNA-Binding Proteins, MESH : Diabetes Mellitus, Experimental, Sterol Regulatory Element Binding Protein 1, medicine.medical_specialty, MESH: Gene Expression, MESH: Gene Transfer Techniques, MESH: Insulin, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Adenoviridae, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 1, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], RNA, Messenger, MESH : Gene Transfer Techniques, MESH : Injections, Intraperitoneal, MESH : Glucose, Glucokinase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH : Gene Expression, Glucose, Endocrinology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], chemistry, CCAAT-Enhancer-Binding Proteins, Mice, Inbred CBA, MESH: Liver, Transcription Factors, MESH : Transcription Factors, MESH : Insulin, MESH : Mice, Inbred CBA, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, chemistry.chemical_compound, MESH: Genetic Vectors, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Diabetes Mellitus, Experimental, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Recombinant Proteins, MESH: Glucose, DNA-Binding Proteins, Liver, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Homeostasis, MESH : Homeostasis, Phosphoenolpyruvate carboxykinase, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, MESH : Recombinant Proteins, MESH : Male, Genetic Vectors, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Diabetes mellitus, Internal medicine, MESH : Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Internal Medicine, medicine, Animals, MESH : Adenoviridae, MESH: Mice, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Liver, Metabolism, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins
Abstract

International audience; In vitro, the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) mimics the positive effects of insulin on hepatic genes involved in glucose utilization, such as glucokinase (GK) and enzymes of the lipogenic pathway, suggesting that it is a key factor in the control of hepatic glucose metabolism. Decreased glucose utilization and increased glucose production by the liver play an important role in the development of the hyperglycemia in diabetic states. We thus reasoned that if SREBP-1c is indeed a mediator of hepatic insulin action, a hepatic targeted overexpression of SREBP-1c should greatly improve glucose homeostasis in diabetic mice. This was achieved by injecting streptozotocin-induced diabetic mice with a recombinant adenovirus containing the cDNA of the mature, transcriptionally active form of SREBP-1c. We show here that overexpressing SREBP-1c specifically in the liver of diabetic mice induces GK and lipogenic enzyme gene expression and represses the expression of phosphoenolpyruvate carboxykinase, a key enzyme of the gluconeogenic pathway. This in turn increases glycogen and triglyceride hepatic content and leads to a marked decrease in hyperglycemia in diabetic mice. We conclude that SREBP-1c has a major role in vivo in the long-term control of glucose homeostasis by insulin.

Published
2001

28. Sterol-regulatory-element-binding protein 1c mediates insulin action on hepatic gene expression

Author

Ferré, P., Foretz, F, Azzout-Marniche, Dalila, Bécard, D, Foufelle, F., Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH : Transcription Factors, MESH : Insulin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: CCAAT-Enhancer-Binding Proteins, MESH : Mammals, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Homeostasis, Insulin, MESH: Animals, MESH : Glycolysis, Mammals, MESH : Gene Expression Regulation, MESH : Glucagon, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Glucagon, MESH: Energy Metabolism, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Gene Expression Regulation, MESH: Glucose, DNA-Binding Proteins, MESH : CCAAT-Enhancer-Binding Proteins, Liver, MESH: Homeostasis, MESH : Homeostasis, MESH: Glycolysis, MESH : DNA-Binding Proteins, Sterol Regulatory Element Binding Protein 1, Glycolysis, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Insulin, MESH: Mammals, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Sterol Regulatory Element Binding Protein 1, MESH : Sterol Regulatory Element Binding Protein 1, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH : Glucose, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Liver, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Glucagon, MESH : Energy Metabolism, Glucose, Gene Expression Regulation, CCAAT-Enhancer-Binding Proteins, MESH : Animals, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, MESH: Liver, Transcription Factors
Abstract

International audience; Effects of insulin on the expression of liver-specific genes are part of the adaptive mechanisms aimed at maintaining energy homeostasis in mammals. When the diet is rich in carbohydrates, secreted insulin stimulates the expression of genes for enzymes involved in glucose utilization (glucokinase, L-type pyruvate kinase and lipogenic enzymes) and inhibits genes for enzymes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes have been poorly understood. Recently, the transcription factor sterol-regulatory-element-binding protein 1c has been proposed as a key mediator of insulin transcriptional effects. Here we review the evidence that has led to this proposal and the consequences for our understanding of insulin effects in physiological or pathological conditions.

Published
2001

29. Characterization of the Role of AMP-Activated Protein Kinase in the Regulation of Glucose-Activated Gene Expression Using Constitutively Active and Dominant Negative Forms of the Kinase

Author

Woods, Angela, Azzout-Marniche, Dalila, Foretz, Marc, Stein, Silvie, Lemarchand, Patricia, Ferré, P., Foufelle, Fabienne, Carling, David, Ferré, Pascal, Hammersmith Hospital, Charing Cross Hospital & Imperial College, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellular Stress Group, Imperial College London-Hammersmith Hospital-Medical Research Council Clinical Sciences Centre, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), FORETZ, Marc, and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
MESH : Cell Line, MESH : Molecular Sequence Data, MESH : Transcription Factors, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Amino Acid Sequence, AMP-Activated Protein Kinases, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Multienzyme Complexes, MESH : Proteins, 0302 clinical medicine, AMP-activated protein kinase, Gene expression, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH : Female, MESH: Animals, MESH: Proteins, MESH: AMP-Activated Protein Kinases, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Regulation of gene expression, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, biology, Kinase, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Amino Acid Sequence, MESH: Gene Expression Regulation, Enzymologic, MESH : AMP-Activated Protein Kinases, Nuclear Proteins, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, MESH : Multienzyme Complexes, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glucose, Biochemistry, Liver, MESH: Pyruvate Kinase, Female, MESH: Fatty Acid Synthases, MESH : Protein-Serine-Threonine Kinases, MESH: Rats, Molecular Sequence Data, Pyruvate Kinase, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein Serine-Threonine Kinases, MESH : Rats, Wistar, Gene Expression Regulation, Enzymologic, MESH: Protein-Serine-Threonine Kinases, MESH : Gene Expression Regulation, Enzymologic, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell Line, 03 medical and health sciences, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Multienzyme Complexes, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Amino Acid Sequence, Rats, Wistar, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein kinase A, Molecular Biology, Transcription factor, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, MESH : Glucose, MESH : Humans, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], AMPK, MESH : Acetyl-CoA Carboxylase, MESH : Liver, MESH : Nuclear Proteins, Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, MESH: Rats, Wistar, MESH : Pyruvate Kinase, Rats, MESH: Cell Line, Glucose, biology.protein, MESH : Animals, MESH: Acetyl-CoA Carboxylase, MESH : Fatty Acid Synthases, Fatty Acid Synthases, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Female, MESH: Nuclear Proteins, 030217 neurology & neurosurgery, Pyruvate kinase, Acetyl-CoA Carboxylase, Transcription Factors, MESH: Liver
Abstract

International audience; In the liver, glucose induces the expression of a number of genes involved in glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and fatty acid synthase. Recent evidence has indicated a role for the AMP-activated protein kinase (AMPK) in the inhibition of glucose-activated gene expression in hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose induction of these genes. In order to study further the role of AMPK in regulating gene expression, we have generated two mutant forms of AMPK. One of these (alpha1(312)) acts as a constitutively active kinase, while the other (alpha1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used adenovirus-mediated gene transfer to express these mutants in primary rat hepatocytes in culture in order to determine their effect on AMPK activity and the transcription of glucose-activated genes. Expression of alpha1(312) increased AMPK activity in hepatocytes and blocked completely the induction of a number of glucose-activated genes in response to 25 mM glucose. This effect is similar to that observed following activation of AMPK by 5-amino-imidazolecarboxamide riboside. Expression of alpha1DN markedly inhibited both basal and stimulated activity of endogenous AMPK but had no effect on the transcription of glucose-activated genes. Our results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway. This study demonstrates that the two mutants we have described will provide valuable tools for studying the wider physiological role of AMPK.

Published
2000
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30. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes

Author

Dalila Azzout-Marniche, Marc Foretz, Fabienne Foufelle, Pascal Ferré, Colette Guichard, Dominique Bécard, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
MESH: Protein Precursors, Transcription, Genetic, medicine.medical_treatment, MESH : Hepatocytes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Hepatocytes, 0302 clinical medicine, Insulin receptor substrate, Insulin, MESH: Animals, Enzyme Inhibitors, MESH : Immunoblotting, Cells, Cultured, Protein Synthesis Inhibitors, 0303 health sciences, MESH : Cell Nucleus, MESH : Glucokinase, MESH: Immunoblotting, food and beverages, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Glucokinase, MESH: Transcription Factors, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, MESH : DNA-Binding Proteins, Sterol Regulatory Element Binding Protein 1, MESH: Cells, Cultured, MESH: Cell Nucleus, MESH: Enzyme Activation, MESH : Cell Membrane, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Insulin, digestive system, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, MESH : Sterol Regulatory Element Binding Protein 1, MESH: Blotting, Northern, Protein Precursors, Molecular Biology, Dose-Response Relationship, Drug, Glucokinase, Endoplasmic reticulum, Cell Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sterol regulatory element-binding protein, Enzyme Activation, MESH: Phosphatidylinositol 3-Kinases, CCAAT-Enhancer-Binding Proteins, MESH: Female, Transcription Factors, MESH: Signal Transduction, Time Factors, MESH : Transcription Factors, MESH : Insulin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Dose-Response Relationship, Drug, Endoplasmic Reticulum, MESH: Dose-Response Relationship, Drug, Phosphatidylinositol 3-Kinases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], polycyclic compounds, MESH : Female, Cycloheximide, MESH: Cycloheximide, MESH : Protein Precursors, MESH : Endoplasmic Reticulum, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Blotting, Northern, DNA-Binding Proteins, Fatty acid synthase, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Enzyme Inhibitors, Female, lipids (amino acids, peptides, and proteins), MESH : Time Factors, Research Article, Signal Transduction, MESH: Rats, Immunoblotting, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Endoplasmic Reticulum, MESH : Cycloheximide, MESH : Cells, Cultured, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH : Protein Synthesis Inhibitors, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Protein Synthesis Inhibitors, MESH: Transcription, Genetic, MESH: Time Factors, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Phosphatidylinositol 3-Kinases, Cell Biology, Blotting, Northern, Rats, biology.protein, Hepatocytes, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, MESH: Cell Membrane
Abstract

International audience; The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of insulin on the transcription of genes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.

Published
2000

31. Action potential-evoked Ca2+ signals and calcium channels in axons of developing rat cerebellar interneurons

Author

Forti, Lia, Pouzat, Christophe, Llano, Isabel, Laboratoire de physiologie cérébrale (LPC - UMR 8118), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pouzat, Christophe, Laboratoire de physiologie cérébrale ( LPC - UMR 8118 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Abstract

1. Axonal [Ca2+] transients evoked by action potential (AP) propagation were studied by monitoring the fluorescence of the high-affinity calcium-sensitive dye Oregon Green 488 BAPTA-1, introduced through whole-cell recording pipettes in the molecular layer of interneurones from cerebellar slices of young rats. 2. The spatiotemporal profile of Ca2+-dependent fluorescence changes was analysed in well-focused axonal stretches a few tens of micrometres long. AP-evoked Ca2+ signals were heterogeneously distributed along axons, with the largest and fastest responses appearing in hot spots on average ~5 µm apart. 3. The spatial distribution of fluorescence responses was independent of the position of the focal plane, uncorrelated to basal dye fluorescence, and independent of dye concentration. Recordings using the low-affinity dye mag-fura-2 and a Cs+-based intracellular solution revealed a similar pattern of hot spots in response to depolarisation, ruling out measurement artefacts or possible effects of inhomogeneous dye distribution in the generation of hot spots. 4. Fluorescence responses to a short train of APs in hot spots decreased by 41-76 % after bath perfusion of omega-conotoxin MVIIC (5-6 µM), and by 17-65 % after application of omega-agatoxin IVA (500 nM). omega-Conotoxin GVIA (1 µM) had a variable, small effect (0-31 % inhibition), and nimodipine (5 µM) had none. Somatically recorded voltage-gated currents during depolarising pulses were unaffected in all cases. These data indicate that P/Q-type Ca2+ channels, and to a lesser extent N-type channels, are responsible for a large fraction of the [Ca2+] rise in axonalhot spots. 5. [Ca2+] responses never failed during low-frequency (

Published
2000

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