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94 results on '"Huc, Laurence"'

51. Stefan Grimm, 1963-2014, a tragic loss for the scientific community Obituary

Author

Mahul-Mellier, A-L, Huc, Laurence, Lemarié, A., Irshad, S., Hwang, M., Datler, C., Pazarentzos, E., Ecole Polytechnique Fédérale de Lausanne (EPFL), Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wellcome Trust Ctr Human Genet, University of Oxford [Oxford], Imperial College London, University of California [San Francisco] (UCSF), University of California, ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Oxford, University of California [San Francisco] (UC San Francisco), and University of California (UC)

Subjects
[SDV] Life Sciences [q-bio], Stefan Grimm, [SDV]Life Sciences [q-bio], 1963-2014, scientific community Obituary, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015
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52. Nuclear factor erythroid 2-related factor-2 activity modulate the differential sensitivity of normal and preneoplasic colonocytes to 4-hydroxynonenal

Author

Dalleau, Sabine, Baradat, Maryse, Gauthier, Thierry, Naud, Nathalie, Keller, Julia, Héliès-Toussaint, Cécile, Pierre, Fabrice H.F., Guéraud, Françoise, Huc, Laurence, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2014

53. The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival

Author

Hardonnière, Kévin, primary, Saunier, Elise, additional, Lemarié, Anthony, additional, Fernier, Morgane, additional, Gallais, Isabelle, additional, Héliès-Toussaint, Cécile, additional, Mograbi, Baharia, additional, Antonio, Samantha, additional, Bénit, Paule, additional, Rustin, Pierre, additional, Janin, Maxime, additional, Habarou, Florence, additional, Ottolenghi, Chris, additional, Lavault, Marie-Thérèse, additional, Benelli, Chantal, additional, Sergent, Odile, additional, Huc, Laurence, additional, Bortoli, Sylvie, additional, and Lagadic-Gossmann, Dominique, additional

Published
2016
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55. Suppression of colon carcinogenesis promotion by cured meat in rats with curcumin is associated with stimulation of detoxification of lipid peroxidation products

Author

Bastide, Nadia, Naud, Nathalie, Huc, Laurence, Guéraud, Françoise, Taché, Sylviane, Nassy, Gilles, Dalleau, Sabine, Corpet, Denis E., Pierre, Fabrice H.F., Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Contaminants & Stress Cellulaire (ToxAlim-COMICS), and Institut du Porc (IFIP)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

56. Intracellular pH, oxidative stress and cell metabolism: a trio which orchestrates cell death in cancer cells

Author

Huc, Laurence, Lemarié A., Tekpli X., ., LAGADIC, DOMINIQUE, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

57. Apc mutation increases metabolization capacities of mouse colonocytes towards the dietary lipid oxidation product 4-hydroxynonenal

Author

Baradat, Maryse, Jouanin, Isabelle, Dalleau, Sabine, Tacher, Sandrine, Gieules, Mathilde, Debrauwer, Laurent, Canlet, Cécile, Huc, Laurence, Dupuy, Jacques, Pierre, Fabrice H.F., Guéraud, Françoise, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

58. Complex II specific dissociation links pH changes to oxidative stress for apoptosis induction

Author

lemarie, A, Huc, Laurence, Pazarentzos, E, Mahul-Mellier, Anne-Laure, Grimm, S, ProdInra, Migration, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

59. Complex II specific dissociation links pH changes to oxidative stress for apoptosis induction

Author

Lemarié, A., Huc, Laurence, Pazarentzos E, Mahul-Mellier Al And Grimm S., ., Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Saisissez le nom du laboratoire, du service ou du département., Ville service., and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2011

60. Role for NHE1 in chemically-induced apoptosis

Author

Huc, Laurence, Tekpli , .X., Rebillard, A., Dimanche-Boitrel, Mt., LAGADIC, DOMINIQUE, ProdInra, Migration, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

61. The acidic extracellular pH : origin, role in tumorigenesis and cancer therapy

Author

Dimanche-Boitrel, Marie-Thérèse, Meurette, Olivier, Jouan-Lanhouet, Sandrine, Rébillard, Amélie, Huc, Laurence, Lagadic-Gossmann, Dominique, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dominique Lagadic-Gossmann, Brébion, Alice, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Published
2011

62. Role for NHE1 in chemically-induced apoptosis In: Proton Homeostasis in Tumorigenesis and cell death processes

Author

Huc, Laurence, Tekpli, Xavier, Rébillard, Amélie, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dominique Lagadic-Gossmann, Brébion, Alice, Université de Rennes (UR), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Published
2011

63. Ahr-dependent lipid membrane remodelling: an early step facilitating benzo[a]pyrene-induced apoptosis

Author

Holme, Jørn A., Tekpli, Xavier, Dendelé, Béatrice, Debure, Laure, Sergent, Odile, Rissel, Maryvonne, Huc, Laurence, Catheline, Daniel, Rioux, Vincent, Legrand, Philippe, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Division of Environmental Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Experimental Medicine and Toxicology, Laboratoire de biochimie, Institut National de la Recherche Agronomique (INRA), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Brébion, Alice

Subjects
[SDV.TOX] Life Sciences [q-bio]/Toxicology, HMG-CoA reductase, Cholesterol-rich microdomains, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Apoptosis, Reactive oxygen species, Aryl hydrocarbon receptor
Published
2010

64. Carcinogen-induced lipid membrane remodelling is essential for the NHE-1 activation involved in related apoptosis

Author

Tekpli, Xavier, Dendelé, Béatrice, Debure, Laure, Sergent, Odile, Rissel, Maryvonne, Huc, Laurence, Catheline, Daniel, Rioux, Vincent, Legrand, Philippe, Holme, Jørn A., Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Interactions cellulaires et moléculaires (ICM), Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Experimental Medicine and Toxicology, Laboratoire de biochimie, Institut National de la Recherche Agronomique (INRA), Division of Environmental Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), Brébion, Alice, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology
Published
2010

65. Membrane remodeling, an early event in benzo a pyrene-induced apoptosis

Author

Tekpli, X., Rissel, M., Huc, Laurence, Catheline, Daniel, Sergent, O., Rioux, Vincent, Legrand, Philippe, Holme, J. A., Dimanche-Boitrel, M. T., Lagadic-Gossmann, D., Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
ppar-alpha, hypolipidemic drugs, delta-6 desaturase, retinoic acid, lipids (amino acids, peptides, and proteins), liver, polyunsaturated fatty-acids, gene-expression, induction, stearoyl-coa desaturase, mouse, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

Benzo[a]pyrene (B[a]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[a]P-induced apoptotic process. In this study, we report that B[a]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[a]P exposure. B[a]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[a]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[a]P-related H(2)O(2) formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[a]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[a]P altered the composition of plasma membrane microstructures through AhR and H(2)O(2) dependent-regulation of lipid biosynthesis. In F258 cells, the B[a]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization. (C) 2009 Elsevier Inc. All rights reserved.

Published
2010

66. Implication des radeaux lipidiques dans l'apoptose induite par le benzo(a)pyrène

Author

Tekpli, Xavier, Rissel, Mary, Huc, Laurence, Catheline, Daniel, Gorria, Morgane, Sergent, Odile, Rioux, Vincent, Legrand, P., Fardel, Olivier, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Brébion, Alice, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Experimental Medicine and Toxicology, Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Published
2008

67. Hexokinase II: a key NHE1- and p53-regulated protein in benzo[a]pyrene-induced apoptosis

Author

Huc, Laurence, Tekpli, Xavier, Holme, Jørn, Solhaug, Anita, Gorria, Morgane, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Division of Environmental Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), Section for Toxicology, National Veterinary Institute, Institute of Public Health, Université de Rennes (UR), and Brébion, Alice

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

68. Rôle des microdomaines membranaires dans la modulation de l'échangeur Na+/H+ au cours de l'apoptose chimio-induite

Author

Tekpli, Xavier, Huc, Laurence, Gorria, Morgane, Rissel, Maryvonne, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR), and Brébion, Alice

Subjects
[SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2006

69. Role for Na+/H+ Exchanger 1 (NHE1) in the Control of Apoptotic Pathways

Author

Lagadic-Gossmann, Dominique, Huc, Laurence, Tekpli, Xavier, Brébion, Alice, C.O. Pickens, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UR)

Subjects
[SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Published
2006

70. Benzo[a]pyrene-induced apoptosis in hepatic epithelial F258 cells through regulation of mitochondrial hexokinase II expression by NHE1 activation

Author

Huc, Laurence, Tekpli, Xavier, Holme, Jørn, Rissel, Maryvonne, Gorria, Morgane, Dimanche-Boitrel, Marie-Thérèse, Lagadic-Gossmann, Dominique, Brébion, Alice, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Division of Environmental Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2006

72. 4-Hydroxy-2(E)-nonenal Metabolism Differs in Apc+/+ Cells and in ApcMin/+ Cells: It May Explain Colon Cancer Promotion by Heme Iron

Author

Baradat, Maryse, primary, Jouanin, Isabelle, additional, Dalleau, Sabine, additional, Taché, Sylviane, additional, Gieules, Mathilde, additional, Debrauwer, Laurent, additional, Canlet, Cécile, additional, Huc, Laurence, additional, Dupuy, Jacques, additional, Pierre, Fabrice H. F., additional, and Guéraud, Françoise, additional

Published
2011
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75. c-Jun NH2-Terminal Kinase–Related Na+/H+ Exchanger Isoform 1 Activation Controls Hexokinase II Expression in Benzo(a)Pyrene-Induced Apoptosis

Author

Huc, Laurence, primary, Tekpli, Xavier, additional, Holme, Jørn A., additional, Rissel, Mary, additional, Solhaug, Anita, additional, Gardyn, Claire, additional, Le Moigne, Gwénaelle, additional, Gorria, Morgane, additional, Dimanche-Boitrel, Marie-Thérèse, additional, and Lagadic-Gossmann, Dominique, additional

Published
2007
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76. Role for cholesterol and caveolin‐rich membrane microdomains in controlling the activity Na+/H+ exchange 1 independently of mitogenic stimulation

Author

HUC, Laurence Therese, primary, Tekpli, Xavier, additional, Lacroix, Jerome, additional, Rissel, Mary, additional, Poët, Mallorie, additional, Noel, Josette, additional, Dimanche‐Boitrel, Marie‐therese, additional, Counillon, Laurent, additional, and Lagadic‐Gossmann, Dominique, additional

Published
2007
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83. Sarcolemmal localisation of Na+/H+ exchange and Na+-HCO3− co-transport influences the spatial regulation of intracellular pH in rat ventricular myocytes.

Author

Garciarena, Carolina D., Ma, Yu‐ling, Swietach, Pawel, Huc, Laurence, and Vaughan‐Jones, Richard D.

Subjects
MUSCLE cells, IMMUNOFLUORESCENCE, CYTOPLASM, SARCOLEMMA, IMMUNOGLOBULINS
Abstract

Key points Acid extrusion from ventricular myocytes typically occurs via Na+/H+ exchange (NHE1) and Na+-HCO3− co-transporters (NBC). This maintains intracellular pH at ∼7.2: The membrane distribution of these transporters is uncertain., Immunofluorescence indicates that: NBC isoforms are located in lateral sarcolemma, intercalated discs and transverse tubules, whereas NHE1 is densely expressed at intercalated discs., Functional experiments with detubulated myocytes indicate reduced acid extrusion on NBC but no effect on NHE1 activity, confirming exclusion of NHE1 function from transverse tubules., Stimulating NHE1 activity induces sub-sarcolemmal [H+]i depletion (forming local pHi microdomains), particularly at intercalated discs, while stimulating NBC activity induces no pHi microdomains., Our results provide the first demonstration that pHi in ventricular myocytes is locally controlled through selective trafficking of membrane ion transporters. NHE1 preferentially controls pHi at intercalated discs, where cell-to-cell gap-junctional channels are located, while NBC influences pHi adjacent to transverse tubules, where key proteins for excitation-contraction coupling are located., Abstract Membrane acid extrusion by Na+/H+ exchange (NHE1) and Na+-HCO3− co-transport (NBC) is essential for maintaining a low cytoplasmic [H+] (∼60 n m, equivalent to an intracellular pH (pHi) of 7.2). This protects myocardial function from the high chemical reactivity of H+ ions, universal end-products of metabolism. We show here that, in rat ventricular myocytes, fluorescent antibodies map the NBC isoforms NBCe1 and NBCn1 to lateral sarcolemma, intercalated discs and transverse tubules (t-tubules), while NHE1 is absent from t-tubules. This unexpected difference matches functional measurements of pHi regulation (using AM-loaded SNARF-1, a pH fluorophore). Thus, myocyte detubulation (by transient exposure to 1.5 m formamide) reduces global acid extrusion on NBC by 40%, without affecting NHE1. Similarly, confocal pHi imaging reveals that NBC stimulation induces spatially uniform pHi recovery from acidosis, whereas NHE1 stimulation induces pHi non-uniformity during recovery (of ∼0.1 units, for 2-3 min), particularly at the ends of the cell where intercalated discs are commonly located, and where NHE1 immunostaining is prominent. Mathematical modelling shows that this induction of local pHi microdomains is favoured by low cytoplasmic H+ mobility and long H+ diffusion distances, particularly to surface NHE1 transporters mediating high membrane flux. Our results provide the first evidence for a spatial localisation of [H+]i regulation in ventricular myocytes, suggesting that, by guarding pHi, NHE1 preferentially protects gap junctional communication at intercalated discs, while NBC locally protects t-tubular excitation-contraction coupling. [ABSTRACT FROM AUTHOR]

Published
2013
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85. Regulation of Na+/H+ exchanger 1 allosteric balance by its localization in cholesterol- and caveolin-rich membrane microdomains.

Author

Tekpli, Xavier, Huc, Laurence, Lacroix, Jérôme, Rissel, Mary, Poët, Mallorie, Noél, Josette, Dimanche-Boitrel, Marie-Thérèse, Counillon, Laurent, and Lagadic-Gossmann, Dominique

Subjects
*TISSUES, *APOPTOSIS, *HYDROGEN-ion concentration, *CHOLESTEROL, *CYCLODEXTRINS, *SERUM, *PROTEIN kinases, *MITOGEN-activated protein kinases
Abstract

The Na+/H+ exchanger 1, which plays an essential role in intracellular pH regulation in most tissues, is also known to be a key actor in both proliferative and apoptotic processes. Its activation by H+ is best described by the Monod–Wyman–Changeux model: the dimeric NHE-1 oscillates between a low and a high affinity conformation, the balance between the two forms being defined by the allosteric constant L0. In this study, influence of cholesterol- and caveolin-rich microdomains on NHE-1 activity was examined by using cholesterol depleting agents, including methyl-β-cyclodextrin (MBCD). These agents activated NHE-1 by modulating its L0 parameter, which was reverted by cholesterol repletion. This activation was associated with NHE-1 relocation outside microdomains, and was distinct from NHE-1 mitogenic and hormonal stimulation; indeed MBCD and serum treatments were additive, and serum alone did not change NHE-1 localization. Besides, MBCD activated a serum-insensitive, constitutively active mutated NHE-1 (625KDKEEEIRK635 into KNKQQQIRK). Finally, the membrane-dependent NHE-1 regulation occurred independently of Mitogen Activated Protein Kinases, especially Extracellular Regulated Kinase activation, although this kinase was activated by MBCD. In conclusion, localization of NHE-1 in membrane cholesterol- and caveolin-rich microdomains constitutes a novel physiological negative regulator of NHE-1 activity. J. Cell. Physiol. 216: 207–220, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Published
2008
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86. Membrane Fluidity Changes Are Associated with Benzo[ a]Pyrene-Induced Apoptosis in F258 Cells.

Author

GORRIA, MORGANE, TEKPLI, XAVIER, SERGENT, ODILE, HUC, LAURENCE, GABORIAU, FRANÇOIS, RISSEL, MARY, CHEVANNE, MARTINE, DIMANCHE‐BOITREL, MARIE‐THÉRÈSE, and LAGADIC‐GOSSMANN, DOMINIQUE

Subjects
BENZOPYRENE, POLLUTANTS, CELL-mediated cytotoxicity, CARCINOGENS, POLYCYCLIC aromatic hydrocarbons, APOPTOSIS, CELL death, TOXICOLOGY
Abstract

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[ a]yrene (B[ a]P) constitute a widely distributed class of environmental pollutants, responsible for highly toxic effects. Elucidating the intracellular mechanisms of this cytotoxicity thus remains a major challenge. Besides the activation of the p53 apoptotic pathway, we have previously found in F258 hepatic cells that the B[ a]P (50 nM)-induced apoptosis was also dependent upon the transmembrane transporter NHE1, whose activation might result from membrane alterations in our model. We here demonstrate that: (1) B[ a]P induces a membrane fluidization surprisingly linked to NHE1 activation; (2) membrane stabilization by exogenous cholesterol protects cells from B[ a]P-induced apoptosis, via an effect on late acidification and iron uptake. [ABSTRACT FROM AUTHOR]

Published
2006
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87. Apoptotic Mitochondrial Dysfunction Induced by Benzo(a)pyrene in Liver Epithelial Cells.

Author

HUC, LAURENCE, GILOT, DAVID, GARDYN, CLAIRE, RISSEL, MARY, DIMANCHE‐BOITREL, MARIE‐THÉRÈSE, GUILLOUZO, ANDRÉ, FARDEL, OLIVIER, and LAGADIC‐GOSSMANN, DOMINIQUE

Subjects
APOPTOSIS, MITOCHONDRIA, EPITHELIAL cells, ORGANELLES, CELL death, PROTOPLASM, EPITHELIUM, EXFOLIATIVE cytology, EXTRACHROMOSOMAL DNA
Abstract

How pHi changes, more specifically alkalinization, affect the apoptotic cascade has yet to be determined. The aim of the present work was to test the involvement of mitochondria in the apoptotic cascade triggered by benzo(a)pyrene [B(a)P] and to determine the role of pHi changes and p53 relative to mitochondria. Our results indicate that B(a)P-induced apoptosis might rely upon a p53-dependent and a pH-sensitive mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Published
2004
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88. Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons.

Author

Huc, Laurence, Sparfel, Lydie, Rissel, Mary, Dimanche-Boitrel, Marie-Thérèse, Guillouzo, André, Fardel, Olivier, and Lagadic-Gossmann, Dominique

Subjects
*POLYCYCLIC aromatic hydrocarbons, *INTRACELLULAR pathogens, *EPITHELIAL cells, *LIVER, *APOPTOSIS
Abstract

Presents a study on the effects of polycyclic aromatic hydrocarbons (PAH) on intracellular pH in liver epithelial cells. Induction of an early intracellular alkalinization by PAH; Involvement of NHE-1-related transient alkalinization in benzo(a)pyrene-induced apoptosis of liver epithelial cells; Conclusion of the study.

Published
2004
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89. H+-extrusion by Na+-H+ exchange is localised at the surface sarcolemma in rat ventricular myocytes.

Author

Therese HUC, Laurence, Swietach, Pawel, Lira, Gregory, Simmonds, Lucy, and Vaughan-Jones, Richard David

Subjects
*SARCOLEMMA, *MUSCLE cells, *HYDROGEN-ion concentration, *IMMUNOFLUORESCENCE, *LABORATORY mice
Abstract

Na+-H+ exchange (NHE) is the principal H+-extrusion mechanism from cardiac cells. We have investigated the spatial location of functionally active NHE in rat isolated ventricular myocytes. Cells were subjected to transient hypertonic shock using 1.5M formamide (Brette et al, Am J Physiol 283; 2002) to disrupt the t-system, and then assayed for NHE-mediated H+-extrusion (using SNARF to monitor pHi recovery following an NH4Cl-prepulse; Hepes-buffered superfusates). Successful detubulation was checked in some cells by membrane staining with di-8-Anneps, and in others by monitoring the electrically evoked Ca2+i-transient (confocal linescan using fluo-3; a sub-sarcolemmal Ca2+i-increase in detubulated myocytes). Both intrinsic buffer capacity and H+-extrusion at a given pHi (7.2-6.2) were unaffected by detubulation, suggesting NHE activity is principally at the sarcolemmal surface. Immunofluorescent staining with NHE1 mouse monoclonal antibody 611775, clone 54 (BD Transduction Laboratories) revealed limited expression at the surface sarcolemma, widespread punctate expression at intracellular sites, but no appearance at t-system sites. We conclude that H+extrusion from the ventricular myocyte is achieved functionally at surface rather than t-system membranes. [ABSTRACT FROM AUTHOR]

Published
2007

90. Identification of the F1-ATPase at the Cell Surface of Colonic Epithelial Cells: ROLE IN MEDIATING CELL PROLIFERATION.

Author

Kowalski-Chauvel, Aline, Najib, Souad, Tikhonova, Irina G., Huc, Laurence, Lopez, Fredéric, Martinez, Laurent O., Cohen-Jonathan-Moyal, Elizabeth, Ferrand, Audrey, and Seva, Catherine

Subjects
*EPITHELIAL cells, *ADENOSINE triphosphatase, *MITOCHONDRIAL membranes, *CELL proliferation, *MASS spectrometry
Abstract

F1 domain of F1F0-ATPase was initially believed to be strictly expressed in the mitochondrial membrane. Interestingly, recent reports have shown that the F1 complex can serve as a cell surface receptor for apparently unrelated ligands. Here we show for the first time the presence of the F1-ATPase at the cell surface of normal or cancerous colonic epithelial cells. Using surface plasmon resonance technology and mass spectrometry, we identified a peptide hormone product of the gastrin gene (glycineextended gastrin (G-gly)) as a new ligand for the F1-ATPase. By molecular modeling, we identified the motif in the peptide sequence (E(E/D)XY), that directly interacts with the F1-ATPase and the amino acids in the F1-ATPase that bind this motif. Replacement of the Glu-9 residue by an alanine in the E(E/D)XY motif resulted in a strong decrease of G-gly binding to the F1-ATPase and the loss of its biological activity. In addition we demonstrated that F1-ATPase mediates the growth effects of the peptide. Indeed, blocking F1-ATPase activity decreases G-glyinduced cell growth. The mechanism likely involves ADP production by the membrane F1-ATPase, which is induced by G-gly. These results suggest an important contribution of cell surface F1-ATPase in the pro-proliferative action of this gastrointestinal peptide. [ABSTRACT FROM AUTHOR]

Published
2012
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91. Nrf2 and AhR in metabolic reprogramming after contaminant exposure

Author

Elisa Boutet-Robinet, Laurence Huc, Dominique Lagadic-Gossmann, Sylvie Bortoli, Chard-Hutchinson, Xavier, PROGRAMME DE RECHERCHE EN ALIMENTATION ET INDUSTRIES ALIMENTAIRES - Stratégies préventives de la cancérogenèse colorectale en production et transformation des viandes - - SECURIVIANDE2010 - ANR-10-ALIA-0014 - ALIA - VALID, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The authors are supported by grants: ITMO Cancer AVIESAN within the framework of the Cancer Plan for METAhCOL (n°17CE041) (SB, EBR, DLG and LH) for NeoMeaTox (n° ENV201213)(LH), for ONCOMETABOTOX (n°P027395) and ANR ALIA SecuriViande (ANR-10-ALIA-14) (LHL)., ANR-10-ALIA-0014,SECURIVIANDE,Stratégies préventives de la cancérogenèse colorectale en production et transformation des viandes(2010), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Huc, Laurence

Subjects
0301 basic medicine, Cell, Biology, Toxicology, Nrf2, 03 medical and health sciences, chemistry.chemical_compound, Detoxification, medicine, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, detoxification, Transcription factor, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, environmental carcinogenesis, AhR, Metabolic reprogramming, Metabolism, respiratory system, Cell biology, 030104 developmental biology, medicine.anatomical_structure, chemistry, Environmental Carcinogenesis, Xenobiotic, Reprogramming, Toxicant
Abstract

International audience; Beside their crucial role in xenobiotic biotransformation, AhR and Nrf2 are involved in the regulation of energetic metabolism. Nrf2, as a cytoprotective transcription factor, supply energy for detoxification and antioxidant response. AhR is ligand-activated transcriptional factor implicated in several physiological function. Following pollutant exposure, it acts as a chemosensor to eliminate harmful chemicals. Altogether, AhR and Nrf2 cooperate to contribute to protective responses upon contaminant exposure, including metabolic remodelling. This fine-tuned energetic coupling with detoxification can lead to prominent dysfunction under a chronic exposure to pollutants, and promote a long-term reprogramming that affects multiple cellular activities. In the article, we review the involvement of Nrf2 and AhR in the metabolic adaptations that occur during the short-term cell defence upon toxicant exposure, and in the metabolic reprogramming caused by their sustained activation. We also provide several clues to highlight the potential role of the Nrf2/AhR-induced metabolic changes in environmental carcinogenesis. © 2017

Published
2018
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92. Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons

Author

Huc, Laurence, Sparfel, Lydie, Rissel, Mary, Dimanche-Boitre, Marie-Thérèse, Guillouzo, André, Fardel, Olivier, and Lagadic-Gossmann, Dominique

Subjects
intracellular pH • benzo(a)pyrene • apoptosis • metabolism
Abstract

The ubiquitous environmental pollutants polycyclic aromatic hydrocarbons are responsible for important carcinogenic and apoptotic effects, whose mechanisms are still poorly understood, owing to the multiplicity of possible cellular targets. Among these mechanisms, alterations of ionic homeostasis have been suggested. In this work, the effects of benzo(a)pyrene [B(a)P] on pHi were tested in the rat liver F258 epithelial cell line, using the fluoroprobe carboxy-SNARF-1. After a 48-h treatment, B(a)P (50 nM) induced an alkalinization, followed by an acidification after 72 h and the development of apoptosis. Determinations of pH(i) recovery following an acid load showed an increased acid efflux at 48 h. Cariporide inhibited both the early alkalinization and the increased acid efflux, thus suggesting the involvement of Na+/H+ exchanger 1 (NHE1). Besides, alpha-naphtoflavone (alpha-NF), an inhibitor of CYP1A1-mediated B(a)P metabolism, prevented all pH(i) changes, and NHE1 activation was blocked by the antioxidant thiourea, which inhibited CYP1A1 metabolism-dependent H2O2 production. Regarding B(a)P-induced apoptosis, this was prevented by alpha-NF and bongkrekic acid, an inhibitor of mitochondria-dependent apoptosis. Interestingly, apoptosis was significantly reduced by cariporide. Taken together, our results indicate that B(a)P, via H2O2 produced by CYP1A1-dependent metabolism, induces an early activation of NHE1, resulting in alkalinization; this appears to play a significant role in mitochondria-dependent B(a)P-induced apoptosis.

Published
2004

93. Validation of Gelbond® high-throughput alkaline and Fpg-modified comet assay using a linear mixed model.

Author

Perdry H, Gutzkow KB, Chevalier M, Huc L, Brunborg G, and Boutet-Robinet E

Subjects
DNA Damage drug effects, DNA-Formamidopyrimidine Glycosylase metabolism, Humans, Hydrophobic and Hydrophilic Interactions, Leukocytes, Mononuclear metabolism, Linear Models, Methyl Methanesulfonate toxicity, Comet Assay methods, High-Throughput Screening Assays methods, Mutagens toxicity, Polyesters chemistry
Abstract

Even if the comet assay has been widely used for decades, there is still a need for controlled studies and good mathematical models to assess the variability of the different versions of this assay and in particular to assess potential intra-experimental variability of the high-throughput comet assay. To address this point, we further validate a high-throughput comet assay that uses hydrophilic polyester film (Gelbond®). Experiments were performed using human peripheral blood mononuclear cells (PBMC) either untreated or treated with different concentration of MMS (methyl methanesulfonate). A positive control for the Fpg (Formamidopyrimidine DNA glycosylase)-modified comet assay (Ro 19-8022 with light) was also included. To quantify the sources of variability of the assay, including intradeposit variability, instead of summarizing DNA damage on 50 cells from a deposit by the mean or median of their percentage DNA tail, we analyzed all logit-transformed data with a linear mixed model. The main source of variation in our experimental data is between cells within the same deposit, suggesting genuine variability in the response of the cells rather than variation caused by technical treatment of cell samples. The second source of variation is the inter-experimental variation (day-to-day experiment); the coefficient of this variation for the control was 13.6%. The variation between deposits in the same experiment is negligible. Moreover, there is no systematic bias because of the position of samples on the Gelbond ® film nor the position of the films in the electrophoresis tank. This high-throughput comet assay is thus reliable for various applications. Environ. Mol. Mutagen. 59:595-602, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Published
2018
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94. Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic hydrocarbons.

Author

Huc L, Sparfel L, Rissel M, Dimanche-Boitrel MT, Guillouzo A, Fardel O, and Lagadic-Gossmann D

Subjects
Animals, Apoptosis drug effects, Benzo(a)pyrene pharmacology, Caspase Inhibitors, Caspases metabolism, Cell Line, Cytochrome P-450 CYP1A1 antagonists & inhibitors, Cytochrome P-450 CYP1A1 metabolism, Epithelial Cells cytology, Epithelial Cells drug effects, Guanidines pharmacology, Hydrogen Peroxide metabolism, Hydrogen-Ion Concentration, Liver cytology, Liver drug effects, Models, Biological, Rats, Sulfones pharmacology, Thiourea pharmacology, Benzo(a)pyrene toxicity, Sodium-Hydrogen Exchangers metabolism
Abstract

The ubiquitous environmental pollutants polycyclic aromatic hydrocarbons are responsible for important carcinogenic and apoptotic effects, whose mechanisms are still poorly understood, owing to the multiplicity of possible cellular targets. Among these mechanisms, alterations of ionic homeostasis have been suggested. In this work, the effects of benzo(a)pyrene [B(a)P] on pHi were tested in the rat liver F258 epithelial cell line, using the fluoroprobe carboxy-SNARF-1. After a 48-h treatment, B(a)P (50 nM) induced an alkalinization, followed by an acidification after 72 h and the development of apoptosis. Determinations of pH(i) recovery following an acid load showed an increased acid efflux at 48 h. Cariporide inhibited both the early alkalinization and the increased acid efflux, thus suggesting the involvement of Na+/H+ exchanger 1 (NHE1). Besides, alpha-naphtoflavone (alpha-NF), an inhibitor of CYP1A1-mediated B(a)P metabolism, prevented all pH(i) changes, and NHE1 activation was blocked by the antioxidant thiourea, which inhibited CYP1A1 metabolism-dependent H2O2 production. Regarding B(a)P-induced apoptosis, this was prevented by alpha-NF and bongkrekic acid, an inhibitor of mitochondria-dependent apoptosis. Interestingly, apoptosis was significantly reduced by cariporide. Taken together, our results indicate that B(a)P, via H2O2 produced by CYP1A1-dependent metabolism, induces an early activation of NHE1, resulting in alkalinization; this appears to play a significant role in mitochondria-dependent B(a)P-induced apoptosis.

Published
2004
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