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1. Imbalance of Circulating Innate Lymphoid Cell Subpopulations in Patients With Septic Shock

Author

Julien Carvelli, Christelle Piperoglou, Jeremy Bourenne, Catherine Farnarier, Nathalie Banzet, Clemence Demerlé, Marc Gainnier, and Frédéric Vély

Subjects
sepsis, septic shock, immunosuppression, sepsis-induced immunosuppression, innate lymphoid cells (ILC), NK cells, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Septic shock, a major cause of death in critical care, is the clinical translation of a cytokine storm in response to infection. It can be complicated by sepsis-induced immunosuppression, exemplified by blood lymphopenia, an excess of circulating Treg lymphocytes, and decreased HLA-DR expression on circulating monocytes. Such immunosuppression is associated with secondary infections, and higher mortality. The effect of these biological modifications on circulating innate lymphoid cells (ILCs) has been little studied.Methods: We prospectively enrolled patients with septic shock (Sepsis-3 definition) in the intensive care unit (ICU) of Timone CHU Hospital. ICU controls (trauma, cardiac arrest, neurological dysfunction) were recruited at the same time (NCT03297203). We performed immunophenotyping of adaptive lymphocytes (CD3+ T cells, CD19+ B cells, CD4+CD25+FoxP3+ Treg lymphocytes), ILCs (CD3−CD56+ NK cells and helper ILCs – ILC1, ILC2, and ILC3), and monocytes by flow cytometry on fresh blood samples collected between 24 and 72 h after admission.Results: We investigated adaptive and innate circulating lymphoid cells in the peripheral blood of 18 patients in septic shock, 15 ICU controls, and 30 healthy subjects. As expected, the peripheral blood lymphocytes of all ICU patients showed lymphopenia, which was not specific to sepsis, whereas those of the healthy volunteers did not. Circulating CD3+ T cells and CD3−CD56+ NK cells were mainly concerned. There was a tendency toward fewer Treg lymphocytes and lower HLA-DR expression on monocytes in ICU patients with sepsis. Although the ILC1 count was higher in septic patients than healthy subjects, ILC2, and ILC3 counts were lower in both ICU groups. However, ILC3s within the total ILCs were overrepresented in patients with septic shock. The depression of immune responses has been correlated with the occurrence of secondary infections. We did not find any differences in ILC distribution according to this criterion.Conclusion: All ICU patients exhibit lymphopenia, regardless of the nature (septic or sterile) of the initial medical condition. Specific distribution of circulating ILCs, with an excess of ILC1, and a lack of ILC3, may characterize septic shock during the first 3 days of the disease.

Published
2019
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2. Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation

Author

Elena Gomez-Massa, Laura Balligand, Christelle Piperoglou, Adeline Crinier, Claire Galambrun, Aranzazu Cruz Adalia, Blandine Vallentin, Guillaume Larid, Frédéric Vély, Vincent Barlogis, Catherine Farnarier, Gérard Michel, Nathalie Banzet, Eric Vivier, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Pharma, European Project: 694502,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,TILC(2017), DUMENIL, Anita, and Targeting Innate Lymphoid Cells - TILC - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2017-01-01 - 2021-12-31 - 694502 - VALID

Subjects
0301 basic medicine, Adult, Male, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, CD34, Graft vs Host Disease, Hematopoietic stem cell transplantation, Disease, Biology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, In vivo, Immunity, medicine, Immunology and Allergy, Humans, Lymphocytes, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Tissue homeostasis, Aged, Retrospective Studies, Innate lymphoid cell, Hematopoietic Stem Cell Transplantation, Cell Biology, Middle Aged, Immunity, Innate, [SDV] Life Sciences [q-bio], body regions, 030104 developmental biology, surgical procedures, operative, 030220 oncology & carcinogenesis, Female
Abstract

Lymphocytes are essential for microbial immunity, tumor surveillance, and tissue homeostasis. However, the in vivo development and function of helper-like innate lymphoid cells (ILCs) in humans remain much less well understood than those of T, B, and NK cells. We monitored hematopoietic stem cell transplantation (HSCT) to determine the kinetics of ILC development in both children and adults. It was found that, unlike NK cells, helper-like ILCs recovered slowly, mirroring the pattern observed for T cells, with normalization achieved at 1 year. The type of graft and the proportion of CD34+ cells in the graft did not significantly affect ILC reconstitution. As HSCT is often complicated by acute or chronic graft-versus-host disease (GVHD), the potential role of ILC subsets in maintaining tissue integrity in these conditions was also analyzed. It was found that GVHD was associated with lower levels of activated and gut-homing NKp44+ ILCP, consistent with a non-redundant role of this ILC subset in preventing this life-threatening disorder in lymphopenic conditions.

Published
2021
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3. THU0001 CIRCULATING INNATE LYMPHOID CELLS IN IGG4-RELATED DISEASE

Author

Aurélie Grados, Catherine Farnarier, Christelle Piperoglou, Benjamin De Sainte Marie, Frédéric Vély, Benjamin Terrier, Nathalie Banzet, Nicolas Schleinitz, Nathalie Costedoat-Chalumeau, Matthieu Groh, Jean-Robert Harlé, and Mikael Ebbo

Subjects
business.industry, medicine.medical_treatment, Innate lymphoid cell, GATA3, Eosinophil, medicine.disease, Peripheral blood mononuclear cell, Cytokine, medicine.anatomical_structure, Fibrosis, Immunology, Medicine, IgG4-related disease, Lymph, skin and connective tissue diseases, business
Abstract

Background: IgG4-related disease (IgG4-RD) is characterized by lymphoplasmacytic infiltrates, IgG4+ plasma cells, fibrosis and frequent ectopic lymphoid structures (ELS). Excessive Th2 cytokines production and role of T follicular helper (Tfh) cells have been reported. Innate cells (ILCs), a heterogeneous population of non-B non-T lymphocytes lacking antigen-specific receptors, are able to produce type 2 cytokines (ILC2s) or to participate to ELS formation (ILC3s) and could contribute to IgG4-RD lesions. Objectives: To analyze circulating blood ILCs in IgG4-RD. Methods: IgG4-RD patients were identified according to the Comprehensive Diagnostic Criteria. Patients treated with steroids or DMARDs within 3 months or rituximab within 6 months prior inclusion were excluded. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. ILCs were defined as lymphoid CD45+Lineage(Lin)-CD127+ cells. Among ILCs, 3 subsets were defined according to CRTH2 and CD117 expression. In some patients, transcription factor expression (T-bet, GATA3, RORγt) as well as cytokine production (IFNγ, IL-4/IL-13, IL-17/IL-22) after different stimulations were analyzed in ILC subsets. Results were compared to healthy controls (HC), correlated to clinical and biological characteristics, and compared before and after treatment. Results: Twenty patients with active untreated IgG4-RD and 30 HC were included. In IgG4-RD group, mean age was 64 years and sex ratio 4:1. Serum IgG4 levels were >1.35 g/l for 85% of patients and median eosinophil count 410/mm3. Most patients (65%) were analyzed at diagnosis. Main organs involved were lymph nodes (n=15), pancreas (n=9), salivary glands (n=8), biliary tree and kidney (n=5), lung and retroperitoneum (n=4), with ≥3 organs involved in 65%. Number of blood ILCs was not modified in IgG4-RD patients (1.2 ± 2.6 x103/ml vs 1.5 ± 1.3 x103/ml in HC, p=0.29; 0.07 ± 0.06% of CD45+ lymphocytes vs 0.09 ± 0.05% in HC, p=0.35). ILC1s, ILC2s, and ILC3s represented respectively 30%, 29% and 32% of total ILCs in HC. IgG4-RD patients presented a decrease in ILC2s (23.8% [12.4-29.3], p=0.04) and ILC3s (21.2% [8.8-28.1], p=0.002) and an increase in ILC1s (54.1% [33.8-68.7], p=0.0009) proportions. ILC2s (274/ml [152-594] vs 554/ml [62-1000], p=0.045) and ILC3s (214/ml [120-620] vs 509/ml [336-908], p=0.04) numbers were decreased in IgG4-RD patients. No correlation was found between number or proportion of total ILCs or any ILCs subsets and clinical or biological characteristics such as age, number of organ involved, IgG4-RD Responder Index or serum IgG4. No correlation was found between Tfh and ILC3s, or between eosinophils and ILC2s numbers. As human ILC3s and ILC2s can convert in vitro into IFNγ producing cells, we explore if ILC plasticity could contribute to ILCs subset distribution observed. GATA3 or RORγT expression by ILC1s was not modified (p=0.29, respectively) in IgG4-RD patients compared to HC. As previously reported, no cytokine production (IFNγ, IL-4/IL-13, IL-17/IL-22) was observed after different stimulations of blood ILCs. Analyzes before and after treatment found no difference in proportion or absolute number of total or subsets of circulating ILCs. Conclusion: Circulating ILC2s and ILC3s are decreased in IgG4-RD. Recruitment of ILC2s or ILC3s in tissues, where they could participate to Th2 cytokine production, ELS formation and fibrosis, needs further investigations. Disclosure of Interests: None declared

Published
2019
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4. Évaluation de l’exposition d’adipocytes humains sous-cutanés en culture aux acides linoléiques conjugués par une approche multi-omique

Author

Romain Bott, Nathalie Banzet, Marie-Christine Alessi, Jean-Charles Martin, Bruno Berthet, Catherine Defoort, and Karima Bencharif

Subjects
obesity, subcutaneous adipocytes, lcsh:TP670-699, Lipidome, metabolomics, Biochemistry, conjugated linoleic acid, Transcriptome, Biological pathway, transcriptomics, Metabolic pathway, chemistry.chemical_compound, Metabolomics, chemistry, Adipogenesis, Adipocyte, Metabolome, lcsh:Oils, fats, and waxes, Food Science
Abstract

Conjugated linoleic acids are 18 carbones fatty acids members comprising a consecutive (conjugated) double bonds system with a various cis/trans geometry sequence, giving rise to at least 16 different isomers. Among those, the t10,c12 isomer has been reported to have anti-obesity properties. We evaluated the biological response of human primary adipose tissue cultured adipocytes to that CLA isomer, alone or present in a commercial mixture, using system biology approaches (primarily transcriptomics and metabolomics). We found that CLA changed the biological activity of at least 45 metabolic pathways at the genomic level, which transcriptional activities was associated to a parallelle metabolome adipocyte change (lipidome upmost) (r2value transcriptome/ metabolome of 0.89). In pairwise analysis, it appeared that 6 of these pathways at the genomic level were tightly associated to the metabolomic response, such as apoptosis, interleukine-6, proteasome, reticulum endoplasmic stress, transcription role of heterochromatine, cell proliferation through EGFR dependent tyrosine kinase, gamma-aminobutyrate receptor. This latter exhibited the most tightly relationship with the metabolome variations in multivariated analysis. One may infer that this pathway is the most targeted by CLA treatment. In conclusion, the implementation of a multi-omic global approach allowed the identification of a set of biological pathways at the genomic level associated to the metabolic balance of CLA-treated adipocytes. All of these pathways are related to insulin-resistance, metabolic syndrome and adipogenesis.

Published
2011
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5. Expression of insect cystein-rich antifungal peptides in transgenic tobacco enhances resistance to a fungal disease

Author

Christine Derpierre, Evelyne François, Manuel Dubald, Marie-Pascale Latorse, Nathalie Banzet, and Philippe Bulet

Subjects
Cercospora nicotianae, biology, Heliothis virescens, Nicotiana tabacum, Transgene, fungi, Saccharomyces cerevisiae, Germ tube, Plant Science, General Medicine, Plant disease resistance, biology.organism_classification, Microbiology, Genetics, Agronomy and Crop Science, Botrytis cinerea
Abstract

Heliomicin (from Heliothis virescens) and drosomycin (from Drosophila melanogaster), two cystein-rich antifungal peptides are produced by insects in response to septic injury. Both exhibit in vitro a rather similar broad-spectrum activity on phytopathogens, but microscopic observations indicate different modes of action. Heliomicin and drosomycin have been expressed in transgenic tobacco under the control of strong constitutive promoters, and targeted to the apoplast using signal peptides of plant origin. A significant enrichment of well-cleaved peptides with the expected molecular weight has been detected in the intercellular space of transgenic leaves. The recombinant peptides, partially purified from transgenic tobacco, exhibited in vitro the same antifungal properties on germination of spores of Botrytis cinerea and germ tube elongation as the recombinant peptides produced in Saccharomyces cerevisiae. Heliomicin and drosomycin expressed in transgenic tobacco confer a minor but statistically significant enhanced resistance to the fungal pathogen Cercospora nicotianae.

Published
2002
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6. Modification de la répartition des cellules lymphoïdes innées auxiliaires circulantes au cours de la maladie associée aux IgG4

Author

M. Ebbo, Aurélie Grados, Matthieu Groh, Eric Vivier, Benjamin Terrier, Jean-Robert Harlé, Frédéric Vély, Christelle Piperoglou, Nathalie Banzet, Nicolas Schleinitz, C. Farnarier, and Nathalie Costedoat-Chalumeau

Subjects
030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Gastroenterology, Internal Medicine, 030212 general & internal medicine
Abstract

Introduction La maladie associee aux IgG4 (IgG4-RD) est une pathologie fibro-inflammatoire polyclonale. Sa physiopathologie reste mal connue. Une production excessive de cytokines de type Th2 a ete rapportee dans le sang peripherique et les tissus de ces patients, dans lesquels des follicules lymphoides tertiaires sont frequemment retrouves. Les cellules lymphoides innees (ILCs) helper sont des populations lymphoides d’identification recente, caracterisees par l’absence d’expression de recepteur specifique de l’antigene. Les ILC1s, ILC2s, et ILC3s, partagent avec les lymphocytes T CD4 helper (Th1, Th2 et Th17) l’expression de facteurs de transcription et la production de cytokines correspondantes. Nous avons etudie les sous-populations d’ILCs dans le sang circulant de patients atteints d’IgG4-RD. Patients et methodes Les patients atteints d’IgG4-RD inclus dans cette etude etaient definis selon les criteres diagnostiques internationaux dits « CDC » [1] . L’analyse etait realisee avant tout traitement. Les cellules mononucleees du sang circulant (PBMC) etaient isolees apres prelevement sanguin, et un immunomarquage permettait de caracteriser les ILC1s : Lin-CD127 + CD117 − CRTH2−, les ILC2s : Lin-CD127 + CRTH2+ et les ILC3s : Lin-CD127 + CD117 + CRTH2− en cytometrie de flux (Fortessa X20, Becton Dickinson). Les donnees etaient analysees avec le logiciel FlowJo. Resultats Les resultats obtenus chez 15 patients avec IgG4-RD active et non traitee sont rapportes. Les resultats obtenus ont ete compares a un groupe controle de 30 sujets sains adultes. L’âge moyen etait de 66 ± 14 ans chez les patients atteints d’IgG4-RD, avec une predominence masculine (sex-ratio 4 :1). Les IgG4 seriques etaient >1,35 g/L chez 93 % des patients, le taux median d’IgE de 257 ± 785 kUI/L et le taux median d’eosinophiles de 400 ± 371/mm3. Les atteintes d’organes etaient variables : ganglionnaires (n = 11), pancreatiques (n = 6), salivaires (n = 5), biliaires (n = 4), pulmonaires (n = 3), retroperitoneales (n = 3), aortiques (n = 2), renale, cutanee, lacrymale, testiculaire et mesenterique (n = 1, respectivement). Le nombre median d’ILCs helper circulantes etait de 1,1 ± 1,3 × 103/mL chez les patients atteints d’IgG4-RD, et de 1,4 ± 1,6 × 103/mL chez les patients controles (p = 0,08). Ces cellules representaient 0,06 ± 0,04 % des lymphocytes CD45+ circulants chez les patients atteints d’IgG4-RD, et 0,07 ± 0,05 % chez les sujets controles (p = 0,26). Les patients atteints d’IgG4-RD presentaient une diminution des proportions d’ILC2s et d’ILC3s (p = 0,04 et p = 0,003 respectivement), associee a une augmentation de la proportion d’ILC1s (p = 0,0007). On notait une diminution significative du nombre d’ILC2s, (p = 0,01) et d’ILC3s, (p = 0,02) chez ces patients. Chez 8 patients atteints d’IgG4-RD, l’analyse des ILCs helper circulantes a pu etre realisee avant et apres traitement. Il n’etait pas note de difference significative entre les proportions et le nombre d’ILC1s, d’ILC2s et d’ILC3s avant et apres traitement avec une grande variabilite inter-individuelle. Discussion Au cours de plusieurs pathologies inflammatoires, l’augmentation dans le sang peripherique du nombre d’ILCs auxiliaires potentiellement pathogenes a ete correlee a l’augmentation du nombre de ces cellules au niveau tissulaire (bronchopneumopathie chronique obstructive pour les ILC1s, asthme, sclerodermie systemique et rhino-sinusite chronique pour les ILC2s ; psoriasis et sclerose en plaque pour les ILC3s). L’absence d’elevation des ILC2s, productrices de cytokines Th2, pourrait dans le cas de l’IgG4-RD evoquer un recrutement de ces cellules au niveau tissulaire. L’augmentation relative de la proportion d’ILC1s, pourrait egalement evoquer une « trans-differenciation » des ILC2s et des ILC3s en ILCs de phenotype « inflammatoire » proche des ILC1s, comme cela a ete rapporte au cours de la maladie de Crohn ou de la BPCO. L’augmentation de la proportion d’ILC1s observee chez les patients atteints d’IgG4-RD pourrait, par ailleurs, en partie contribuer a l’augmentation de production d’IFNγ rapportee. Conclusion Une expansion des ILC1s circulantes et une diminution du nombre d’ILC2s et d’ILC3s est observee dans le sang peripherique des patients atteints d’IgG4-RD. Des analyses fonctionnelles et tissulaires de ces cellules permettront de mieux preciser leur role dans la physiopathologie de la maladie associee aux IgG4.

Published
2017
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7. Contrasting effects of NO and peroxynitrites on HSP70 expression and apoptosis in human monocytes

Author

J. F. Dhainaut, Christoph Richter, Christophe Adrie, Barbara S. Polla, Marie-Jeanne Richard, Dominique François, Maria Bachelet, Nathalie Banzet, and A. Tuan Dinh-Xuan

Subjects
inorganic chemicals, Programmed cell death, Physiology, Radical, Apoptosis, Biology, Nitric Oxide, Monocytes, Nitric oxide, Superoxide dismutase, chemistry.chemical_compound, medicine, Humans, HSP70 Heat-Shock Proteins, Cells, Cultured, Nitrates, Superoxide, Monocyte, Free Radical Scavengers, Cell Biology, Oxidants, medicine.anatomical_structure, chemistry, Biochemistry, cardiovascular system, biology.protein, Peroxynitrite
Abstract

The free radicals nitric oxide (·NO) and superoxide (O2 −·) react to form peroxynitrite (ONOO−), a highly toxic oxidant species. In this study we investigated the respective effects of NO and ONOO− in monocytes from healthy human donors. Purified monocytes were incubated for 6 or 16 h with a pure NO donor ( S-nitroso- N-acetyl-dl-penicillamine, 0–2 mM), an ·NO/ONOO− donor (3-morpholinosydnonimine chlorhydrate, 0–2 mM) with and without superoxide dismutase (200 IU/ml), or pure ONOO−. We provide evidence that 3-morpholinosydnonimine chlorhydrate alone represents a strong stress to human monocytes leading to a dose-dependent increase in heat shock protein-70 (HSP70) expression, mitochondrial membrane depolarization, and cell death by apoptosis and necrosis. These phenomena were abolished by superoxide dismutase, suggesting that ONOO−, but not ·NO, was responsible for the observed effects. This observation was further strengthened by the absence of a stress response in cells exposed to S-nitroso- N-acetyl-dl-penicillamine. Conversely, exposure of cells to ONOO− alone also induced mitochondrial membrane depolarization and cell death by apoptosis and necrosis. Thus ONOO− formation may well explain the toxic effect generally attributed to ·NO.

Published
2000
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8. Accumulation of small heat shock proteins, including mitochondrial HSP22, induced by oxidative stress and adaptive response in tomato cells

Author

Christiane Richaud, Michael Kazmaier, Yves Deveaux, Christian Triantaphylidès, Nathalie Banzet, and Jean Gagnon

Subjects
Hot Temperature, Molecular Sequence Data, Plant Science, Oxidative phosphorylation, Mitochondrion, Biology, chemistry.chemical_compound, Solanum lycopersicum, Heat shock protein, Complementary DNA, Gene expression, Genetics, Protein biosynthesis, Electrophoresis, Gel, Two-Dimensional, Amino Acid Sequence, RNA, Messenger, Heat shock, Heat-Shock Proteins, Plant Proteins, Sequence Homology, Amino Acid, Cell Biology, Adaptation, Physiological, Mitochondria, Kinetics, Oxidative Stress, Digitonin, Biochemistry, chemistry, RNA, Plant
Abstract

Changes in gene expression, by application of H2O2, O2.- generating agents (methyl viologen, digitonin) and gamma irradiation to tomato suspension cultures, were investigated and compared to the well-described heat shock response. Two-dimensional gel protein mapping analyses gave the first indication that at least small heat shock proteins (smHSP) accumulated in response to application of H2O2 and gamma irradiation, but not to O2.- generating agents. While some proteins seemed to be induced specifically by each treatment, only part of the heat shock response was observed. On the basis of Northern hybridization experiments performed with four heterologous cDNA, corresponding to classes I-IV of pea smHSP, it could be concluded that significant amounts of class I and II smHSP mRNA are induced by H2O2 and by irradiation. Taken together, these results demonstrate that in plants some HSP genes are inducible by oxidative stresses, as in micro-organisms and other eukaryotic cells. HSP22, the main stress protein that accumulates following H2O2 action or gamma irradiation, was also purified. Sequence homology of amino terminal and internal sequences, and immunoreactivity with Chenopodium rubrum mitochondrial smHSP antibody, indicated that the protein belongs to the recently discovered class of plant mitochondrial smHSP. Heat shock or a mild H2O2 pretreatment was also shown to lead to plant cell protection against oxidative injury. Therefore, the synthesis of these stress proteins can be considered as an adaptive mechanism in which mitochondrial protection could be essential.

Published
1998
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9. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples

Author

Romain Bott, Line Manens, Nathalie Banzet, Gaëlle Favé, Stéphane Grison, Isabelle Dublineau, Catherine Defoort, Eric Blanchardon, Patrick Gourmelon, Maâmar Souidi, Jean-Charles Martin, Olivia Delissen, Jocelyne Aigueperse, Matthieu Maillot, PRP-HOM/SRBE/LRTOX, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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), Institut de Radioprotection et de Surete Nucleaire (IRSN), ProdInra, Migration, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Population, Low-dose, chemistry.chemical_element, Urine, 010501 environmental sciences, Pharmacology, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Medicine, Ingestion, Chronic, education, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, education.field_of_study, Nicotinamide, business.industry, Uranium, Natural uranium, Contamination, 3. Good health, [SDV] Life Sciences [q-bio], N-methylnicotinamide, chemistry, Original Article, business
Abstract

Because uranium is a natural element present in the earth’s crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC–MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure. Electronic supplementary material The online version of this article (doi:10.1007/s11306-013-0544-7) contains supplementary material, which is available to authorized users.

Published
2013
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10. Can we trust untargeted metabolomics: results of the metabo-ring study

Author

Alexandre Verdu, Bernard Lyan, Carole Migne, Catherine Defoort, Cecile Canlet, Christophe Junot, Claude Guillou, Claudine Manach, Christophe Cordella, Daniel Jacob, Delphine Bouveresse, Douglas Rutledge, Estelle Rathahao, Estelle Pujos-Guillot, Fabien Jourdan, Franck Giacomoni, Frédérique Courant, Gaëlle Fave, Gwenaëlle Le Gall, Hubert Chassaigne, Jean-Charles Martin, Jean-Claude Tabet, Jean-Philippe Antignac, Laetitia Shintu, Marianne Defernez, Marie Cécile Alexandre-Gouabau, Marie Josephe Amiot-Carlin, Mathilde Bossis, Mathieu Maillot, Triba, Mohamed N., Natali Stojiljkovic, Nathalie Banzet, Roland Molinié, Romain Bott, Sophie Goulitquer, Stefano Caldarelli, Thomas Moyon, Bruker, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), 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), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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 National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-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), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Joint Research Centre - Institute for Health and Consumer Protection, European Commission, Ingénierie Procédés Aliments (GENIAL), Institut National de la Recherche Agronomique (INRA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Institute of Food Research, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Laboratoire CSPBAT, Université Paris 13 (UP13), Laboratoire des Courses Hippiques (LCH), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV), Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-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), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Fédération Nationale des Courses Françaises, 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), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), HESAM Université (HESAM)-HESAM Université (HESAM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biologie des Plantes et Innovation (BIOPI), Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), UMR A 1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes (UN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), and Avignon Université (AU)-Institut National de la Recherche Agronomique (INRA)

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

Can we trust untargeted metabolomics: results of the metabo-ring study. 2. African-European Conference on Chemometrics - Afrodata 2012

Published
2012

11. Peut-on faire confiance à la métabolomique: résultats de l'initiative MetaboRing

Author

Alexandre Verdu, Bernard Lyan, Carole Migne, Catherine Defoort, Cecile Canlet, Christophe Junot, Claude Guillou, Claudine Manach, Christophe Cordella, Daniel Jacob, Delphine Bouveresse, Douglas Rutledge, Estelle Rathahao, Estelle Pujos-Guillot, Fabien Jourdan, Franck Giacomoni, Frédérique Courant, Gaëlle Fave, Gwénaëlle Le Gall, Hubert Chassaigne, Jean-Charles Martin, Jean Claude Tabet, Jean-Philippe Antignac, Laetitia Shintu, Marianne Defernez, Marie Josephe Amiot-Carlin, Mathilde Bossis, Mathieu Maillot, Triba, Mohamed N., Stojilkovic, N., Nathalie Banzet, Roland Molinié, Romain Bott, Sophie Goulitquer, Stefano Caldarelli, Thomas MOYON, Bruker, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, 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), MetaToul AXIOM (E20), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-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), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Joint Research Center, Institue for Health and Consumer Protection, European Commission, Ingénierie Procédés Aliments (GENIAL), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institute for Food Research, European Commission's Joint Research Centre, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Courses Hippiques (LCH), Fédération Nationale des Courses Françaises, Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboMer, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), 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), 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)-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), Institut National de la Recherche Agronomique (INRA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Université de Picardie Jules Verne (UPJV), Physiologie des Adaptations Nutritionnelles (PhAN), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), 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), 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), HESAM Université (HESAM)-HESAM Université (HESAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, UMR 7244 Laboratoire CSPBAT, Université Paris 13 (UP13), EA 3900 BIOPI Biologie des Plantes Innovation, Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), UMR A 1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes (UN), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), and Avignon Université (AU)-Institut National de la Recherche Agronomique (INRA)

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

Peut-on faire confiance à la métabolomique: résultats de l'initiative MetaboRing. 6. Journées Scientifiques du Réseau Français de Métabolomique et Fluxomique (RFMF)

Published
2012

12. The Metabolomic Approach Identifies a Biological Signature of Low-dose Chronic Exposure to Cesium 137

Author

Jean-Charles Martin, Stéphane Grison, Catherine Defoort, Line Grandcolas, Isabelle Dublineau, Patrick Gourmelon, Gaëlle Favé, Romain Bott, Maâmar Souidi, Nathalie Banzet, Elie Tourlonias, Eric Blanchardon, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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), Institut de Radioprotection et de Surete Nucleaire (IRSN), Electricite de France (EDF), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Migration

Subjects
Male, Health, Toxicology and Mutagenesis, Metabolite, [SDV]Life Sciences [q-bio], Physiology, CHILDREN, Urine, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Tissue Distribution, Cesium 137, Chronic ingestion, biomarker, Metabolomics, Low-doses, CHRONIC CONTAMINATION, CHERNOBYL ACCIDENT, CHOLESTEROL-METABOLISM, CHRONIC INGESTION, RADIATION, RATS, (137)CESIUM, MICE, RADIONUCLIDE, 0303 health sciences, Contamination, 3. Good health, [SDV] Life Sciences [q-bio], Radiation Injuries, Experimental, Dose–response relationship, Cesium Radioisotopes, Prenatal Exposure Delayed Effects, 030220 oncology & carcinogenesis, Environmental chemistry, Biomarker (medicine), Female, Analysis of variance, Water Pollutants, Radioactive, Urinary system, Biology, Models, Biological, 03 medical and health sciences, Animals, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, Drinking Water, Dose-Response Relationship, Radiation, Blood Cell Count, Chernobyl Nuclear Accident, chemistry, 13. Climate action, Biomarkers
Abstract

International audience; Reports have described apparent biological effects of Cs-137 (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to Cs-137 through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated Cs-137-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators.

Published
2012
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13. Thermodynamic study of β-galactosidase for high pressure separation processes

Author

Jean-Louis Saldana, Irmgard Heiber-Langer, Claude Balny, Pierre Lemay, and Nathalie Banzet

Subjects
Volume (thermodynamics), β d galactosidase, Chemistry, Vapor pressure, High pressure, Kinetics, Extrapolation, Thermodynamics, Physical chemistry, Separation method, Pressure dependence, Applied Microbiology and Biotechnology, Biochemistry
Abstract

The reaction of β-galactosidase with o-nitrophenyl-\-D-galactopyranoside was studied as a function of pressure and temperature. The observed activation volume was strongly dependent on the temperature. The calculation of the Maxwell relationships as well as the extrapolation of the pressure dependence f the In Vo versus pressure curves show that the system is thermodynamically consistent.

Published
1993
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14. Circulating endothelial cell count as a diagnostic marker for non-ST-elevation acute coronary syndromes

Author

Jean-Baptiste Meynard, Nathalie Banzet, José Sampol, Murielle Mutin, Jean-Louis Bonnet, Philippe Paule, Jacques Quilici, Pierre Ambrosi, and Françoise Dignat-George

Subjects
Male, medicine.medical_specialty, Time Factors, Endothelium, Circulating endothelial cell, Myocardial Ischemia, Cell Count, Chest pain, Sensitivity and Specificity, Coronary artery disease, Physiology (medical), Internal medicine, Troponin I, medicine, Humans, Aged, Vascular disease, business.industry, ST elevation, Middle Aged, medicine.disease, medicine.anatomical_structure, Circulating Endothelial Cell Count, ROC Curve, Area Under Curve, Acute Disease, cardiovascular system, Cardiology, Female, Endothelium, Vascular, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Background— Shedding of endothelial cells from damaged endothelium into the blood occurs in a variety of vascular disorders. The purpose of this study was to evaluate the utility of circulating endothelial cell (CEC) count as a diagnostic marker of non–ST-elevation acute coronary syndromes (ACSs). Methods and Results— CEC counts were determined immediately (H0), 4 hours (H4), and 8 hours (H8) after admission in 60 patients with documented non–ST-elevation ACS and 40 control patients with no evidence of coronary artery disease. A total of 32 patients in the ACS group had elevated CEC counts (>3 cells/mL) in relation to early admission and single-episode chest pain. Patients from the control group had normal CEC counts. The interval between the chest pain episode and elevation was significantly shorter for CEC than troponin I. No correlation was found between the 2 markers. Interestingly, a subgroup of ACS patients with initially normal troponin I levels had high CEC counts, thus allowing early diagnosis in 30% more cases. At H0, the mean area under the receiver operating characteristic curve was significantly higher with the CEC count than with the troponin I level. At H4 and H8, the combined use of CEC and troponin was significantly better as a marker of ACS than CEC alone or troponin I alone. Conclusions— This study demonstrates that CEC count can be used as an early, specific, independent diagnostic marker for non–ST-elevation ACS. A combined strategy using CEC count and troponin I level could provide an effective diagnostic tool.

Published
2004

15. Tobacco smoke induces mitochondrial depolarization along with cell death: effects of antioxidants

Author

Barbara S. Polla, Dominique François, and Nathalie Banzet

Subjects
Programmed cell death, Physiology, Clinical Biochemistry, Mitochondrion, Cysteine Proteinase Inhibitors, medicine.disease_cause, Biochemistry, Tobacco smoke, Antioxidants, Monocytes, Amino Acid Chloromethyl Ketones, Membrane Potentials, Superoxide dismutase, medicine, Humans, Carcinogen, Cells, Cultured, chemistry.chemical_classification, Reactive oxygen species, biology, Cell Death, Superoxide Dismutase, Biochemistry (medical), Cell Biology, Free Radical Scavengers, Cell biology, Acetylcysteine, Mitochondria, chemistry, Apoptosis, biology.protein, Tobacco Smoke Pollution, Oxidative stress
Abstract

Smoking has been associated with a large number of diseases, in particular cancers. Among the many substances identified in tobacco smoke, reactive oxygen species (ROS) are major carcinogens. We have previously reported that exposure of mammalian cells to tobacco smoke induces the expression of stress proteins, as well as apoptosis (programmed cell death). Here we examined the effects of tobacco smoke on mitochondrial membrane potential (deltapsim), since mitochondria have been proposed to control the effector phase of apoptosis. We used normal human monocytes for these experiments, with the prospect for application of deltapsim as a biomarker of oxidative stress. Tobacco smoke induced mitochondrial depolarization at 3 h, and apoptosis (or necrosis for higher concentrations) after 16 h. Apoptosis was assessed by both a functional approach (annexin V binding) and morphological analysis (electron microscopy). N-acetyl-cysteine prevented tobacco smoke-induced deltapsim disruption and apoptosis, while the caspase inhibitor Z-VAD.Fmk did not affect deltapsim, though preventing apoptosis, and superoxide dismutase had no effect. Our data designate mitochondria as a target for ROS-mediated effects of tobacco smoke exposure.

Published
2000

16. Tobacco smoke induces both apoptosis and necrosis in mammalian cells: differential effects of HSP70

Author

Muriel Vayssier, Barbara S. Polla, Dominique François, Nathalie Banzet, and Kerstin Bellmann

Subjects
Pulmonary and Respiratory Medicine, Programmed cell death, Necrosis, Physiology, DNA damage, Apoptosis, Biology, medicine.disease_cause, Protein oxidation, Cell Line, Euchromatin, Physiology (medical), Heat shock protein, Heterochromatin, Smoke, medicine, Animals, Humans, HSP70 Heat-Shock Proteins, Cell Nucleus, Smoking, Cell Biology, U937 Cells, Chromatin, Hsp70, Genes, bcl-2, Mitochondria, Kinetics, Microscopy, Electron, Proto-Oncogene Proteins c-bcl-2, Immunology, Cancer research, medicine.symptom, Oxidative stress, Cell Nucleolus
Abstract

Tobacco smoke (TS) has been implicated as a major risk factor in human pulmonary diseases including cancer. In this study, we used TS as a model of oxidative stress. TS-mediated oxidative stress has been shown to induce protein oxidation, DNA damage, and cell death. Here we investigated, in human and rodent cell lines, whether TS induces cell death by apoptosis or by necrosis. As described for classic oxidants, TS induced apoptosis at low concentrations and necrosis at higher concentrations. We have previously described the induction of heat shock (HS) protein (HSP) (in particular, HSP70) in human monocytes exposed to TS. HSP70 is implicated in the regulation of cell injury and cell death and, in particular, modulates apoptosis, as does the antiapoptotic oncoprotein Bcl-2. At both apoptotic and necrotic concentrations, TS induced a dose-dependent HSP70 expression, whereas Bcl-2 was induced only at necrotic concentrations. TS- or HS-induced HSP had no protective effects either on apoptosis or on necrosis, but HSP70 overexpression prevented TS-induced necrosis and consequently led to increased apoptosis. These results might reconcile the apparently contradictory data previously reported on the effects of HSP on apoptosis.

Published
1998

17. Molecular Biomarkers of Early Responses to Environmental Stressors: Implications for Risk Assessment and Public Health

Author

S. Kreps, Barbara S. Polla, David C. Christiani, and Nathalie Banzet

Subjects
medicine.medical_specialty, Health (social science), business.industry, Public health, Stressor, Public Health, Environmental and Occupational Health, Environmental Exposure, Risk Assessment, Pollution, Molecular biomarkers, Xenobiotics, Environmental health, Humans, Medicine, Public Health, Environmental Pollution, Epidemiologic Methods, business, Risk assessment, Biomarkers
Published
1997
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