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5 results on '"Emilie Obre"'

1. Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells

Author

Caroline Jose, Etienne Hebert-Chatelain, Nivea Dias Amoedo, Emmanuel Roche, Emilie Obre, Didier Lacombe, Hamid Reza Rezvani, Philippe Pourquier, Karine Nouette-Gaulain, and Rodrigue Rossignol

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells. Keywords: Prostate cancer, Levobupivacaine, Glycolysis, Oxidative phosphorylation, Wortmannin

Published
2018
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2. Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas

Author

Isabelle Redonnet-Vernhet, Nadège Bellance, Floriant Bellvert, Matthieu Thumerel, Nathalie Dugot-Senan, Mariana Figueiredo Rodrigues, Hamid Reza Rezvani, Hugues Begueret, Elodie Dumon, Fatima Mechta-Grigoriou, Rodrigue Rossignol, Didier Lacombe, Pauline Esteves, Giuseppe Punzi, Yann Kieffer, Julien Izotte, Nivea Dias Amoedo, Ciro Leonardo Pierri, Tony Lionel Palama, Saharnaz Sarlak, Benoit Rousseau, Jean-Marc Baste, Lara Gales, Stéphane Claverol, Emilie Obre, Alexis Dupis, Laetitia Dard, Véronique Guyonnet-Duperat, Walid Mafhouf, Cellomet [CHU Pellegrin, Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU de Bordeaux, Università degli studi di Bari Aldo Moro (UNIBA), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Proteomics Core Facility (Protim), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Plateforme Génomique Santé Biogenouest®, Institut National de la Sante et de la Recherche Medicale (Inserm), National Council for Scientific and Technological Development (CNPq), Fondation ARC, French National Institute against cancer (Inca), Ligue nationale contre le cancer, ITN Marie Curie TRANSMIT (H2020-MSCA-ITN-2016) 722605, SIRIC-Brio2 (Project PRIME/IMS/COMMUCAN), CAPES, Canceropole GSO (Club Metabo-Cancer), Plan Cancer, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), TBM-Core [Bordeaux] (UMS3427 - INSERM US005), Université de Rennes (UR)-Plateforme Génomique Santé Biogenouest®, Astruc, Suzette, Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005)

Subjects
0301 basic medicine, Lung Neoplasms, Bioenergetics, Trimetazidine, Oxidative phosphorylation, Mitochondrial trifunctional protein, 03 medical and health sciences, 0302 clinical medicine, Drug Delivery Systems, In vivo, Cell Line, Tumor, medicine, Humans, Beta oxidation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Electron Transport Complex I, biology, Chemistry, Cancer, General Medicine, medicine.disease, 3. Good health, Neoplasm Proteins, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Adenocarcinoma, Mitochondrial Trifunctional Protein, alpha Subunit, Oxidation-Reduction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Research Article
Abstract

International audience; Metabolic reprogramming is a common hallmark of cancer, but a large variability in tumor bioenergetics exists between patients. Using high-resolution respirometry on fresh biopsies of human lung adenocarcinoma, we identified 2 subgroups reflected in the histologically normal, paired, cancer-adjacent tissue: high (OX+) mitochondrial respiration and low (OX-) mitochondrial respiration. The OX+ tumors poorly incorporated [F-18]fluorodeoxy-glucose and showed increased expression of the mitochondrial trifunctional fatty acid oxidation enzyme (MTP; HADHA) compared with the paired adjacent tissue. Genetic inhibition of MTP altered OX+ tumor growth in vivo. Trimetazidine, an approved drug inhibitor of MTP used in cardiology, also reduced tumor growth and induced disruption of the physical interaction between the MTP and respiratory chain complex I, leading to a cellular redox and energy crisis. MTP expression in tumors was assessed using histology scoring methods and varied in negative correlation with [F-18]fluorodeoxy-glucose incorporation. These findings provide proof-of-concept data for preclinical, precision, bioenergetic medicine in oxidative lung carcinomas.

Published
2021
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3. Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2

Author

Emilie Obre, Jean-François Moreau, Rodrigue Rossignol, Christelle Harly, Benoit Viollet, Angela Pappalardo, Vincent Pitard, Isabelle Soubeyran, Charlotte Domblides, Fiyaz Mohammed, Stéphane Claverol, Omar Hawchar, Sonia Netzer, Carla Cano, Layal Massara, Julie Déchanet-Merville, Carrie R. Willcox, Lydia Lartigue, Charlotte Mannat, S.P. Joyce, Benjamin Faustin, Isabelle Mahouche, Thomas Bachelet, Benjamin E. Willcox, Lionel Couzi, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Birmingham [Birmingham], TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Cellomet [CHU Pellegrin, Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, ImCheck Therapeutics [Marseille], Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Janssen Research & Development, Bernardo, Elizabeth, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
0301 basic medicine, T cell, CD3, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, AMP-Activated Protein Kinases, Cell Line, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, medicine, Ephrin, Animals, Humans, Antigens, Intraepithelial Lymphocytes, Tissue homeostasis, Mice, Knockout, Receptor, EphA2, T-cell receptor, AMPK, Antibodies, Monoclonal, Receptors, Antigen, T-Cell, gamma-delta, General Medicine, EPH receptor A2, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer cell, biology.protein
Abstract

International audience; Human γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer.

Published
2021
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4. Metabolic Reprogramming in Amyotrophic Lateral Sclerosis

Author

Rodrigue Rossignol, Emilie Obre, G. Le Masson, Marc Bonneu, Didier Lacombe, C. Léger, Marion Szelechowski, L. Allard, Stéphane Claverol, S. Oliet, Nivea Dias Amoedo, S. Chevallier, Oliet, Stephane, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellomet [CHU Pellegrin, Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), and Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2]

Subjects
0301 basic medicine, Proteome, Bioenergetics, Cell Survival, lcsh:Medicine, Oxidative phosphorylation, Biology, Article, Oxidative Phosphorylation, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, medicine, Animals, Humans, TRNA aminoacylation, Uncoupling Protein 2, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Viability assay, Amyotrophic lateral sclerosis, Cell adhesion, lcsh:Science, Beta oxidation, Skin, Motor Neurons, Multidisciplinary, Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Fatty Acids, lcsh:R, Fibroblasts, medicine.disease, Cell biology, Disease Models, Animal, 030104 developmental biology, Spinal Cord, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Q, Oxidation-Reduction, 030217 neurology & neurosurgery
Abstract

Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients’ skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients’ skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes.

Published
2018
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5. Targeting the mitochondrial trifunctional protein in oxidative lung carcinomas

Author

Rossignol, Rodrigue, Nivea, Amoedo Dias, Emilie, Obre, Hugues, Bégueret, Yann, Kieffer, Benoît, Rousseau, Alexis, Dupis, Nadège, Bellance, Julien, Izotte, Laetitia, Dard, Isabelle, Redonnet-Vernhet, Giuseppe, Punzi, Mariana, Figueiredo Rodrigues, Dumon, Elodie, Walid, Mafhouf, Lara, Gales, Tony, Palama, Floriant, Bellevert, Dugot-Senan, Nathalie, Stéphane, Claverol, Marc, Bonneu, Jean-Marc, Baste, Didier, Lacombe, Reza, Rezvani Hamid, Ciro-Leonardo, Pierri, Fatima, Mechta-Grigoriou, and Mathieu, Thumerel

Published
2018
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