Search

Your search keyword '"MESH: Copper"' showing total 53 results
Start Over Descriptor "MESH: Copper"
53 results on '"MESH: Copper"'

1. Secreted pectin monooxygenases drive plant infection by pathogenic oomycetes

Author

Michael Csukai, Paul H. Walton, Lydia Welsh, Anna O. Avrova, Peter J. Lindley, Neil C. Bruce, Bernard Henrissat, Julie Squires, Gideon J. Davies, Stephen C. Whisson, Simon J. McQueen-Mason, Federico Sabbadin, Saioa Urresti, Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of York [York, UK], Instituto Biofisika, and Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)

Subjects
Models, Molecular, MESH: Oxidation-Reduction, 0106 biological sciences, Protein Conformation, [SDV]Life Sciences [q-bio], 01 natural sciences, Mixed Function Oxygenases, MESH: Protein Conformation, MESH: Plant Diseases, Solanum lycopersicum, MESH: Lycopersicon esculentum, Pathogen, 2. Zero hunger, Oomycete, 0303 health sciences, Multidisciplinary, biology, food and beverages, MESH: Mixed Function Oxygenases, MESH: Copper, MESH: Plant Leaves, Lytic cycle, Phytophthora infestans, Pectins, MESH: Protein Domains, Oxidation-Reduction, MESH: Models, Molecular, Virulence Factors, Virulence, MESH: Solanum tuberosum, Microbiology, Cell wall, 03 medical and health sciences, Protein Domains, Polysaccharides, Gene, Plant Diseases, Solanum tuberosum, MESH: Virulence Factors, 030304 developmental biology, Host (biology), fungi, biology.organism_classification, Plant Leaves, MESH: Polysaccharides, MESH: Phytophthora infestans, Copper, MESH: Pectins, 010606 plant biology & botany
Abstract

Potato pectin falls to Phytophthora Phytophthora infestans is a plant oomycete pathogen that drove the potato famines of the 1800s and continues to afflict potato fields today. The polysaccharide pectin makes up about a third of the cell wall in potatoes. Sabbadin et al . identified a family of lytic polysaccharide monooxygenases (LMPOs) that cleave pectin and are upregulated in P. infestans during infection. Silencing the relevant LMPO gene successfully inhibited P. infestans infections. These findings open doors for disease intervention targets and for biotech applications. —PJH

Published
2021

2. Reclassification of Haloactinobacterium glacieicola as Occultella glacieicola gen. nov., comb. nov., of Haloactinobacterium album as Ruania alba comb. nov, with an emended description of the genus Ruania, recognition that the genus names Haloactinobacterium and Ruania are heterotypic synonyms and description of Occultella aeris sp. nov., a halotolerant isolate from surface soil sampled at an ancient copper smelter

Author

Johann Michael Köhler, Rüdiger Pukall, Dominique Clermont, Meina Neumann-Schaal, Peter Schumann, Jialan Cao, Brian J. Tindall, Jan P. Meier-Kolthoff, Alexis Criscuolo, Franziska Kalensee, Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), Technische Universität Ilmenau (TU ), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collection de l'Institut Pasteur (CIP), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)

Subjects
MESH: Sequence Analysis, DNA, Sequence analysis, Rhamnose, [SDV]Life Sciences [q-bio], Biology, Microbiology, Ruaniaceae, MESH: Bacterial Typing Techniques, 03 medical and health sciences, chemistry.chemical_compound, Type (biology), Ruania, MESH: Base Composition, Genus, Botany, polyphasic taxonomy, sp. nov, MESH: Phylogeny, Nomenclature, MESH: Germany, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, chemistry.chemical_classification, Occultella aeris gen. nov, MESH: Phospholipids, 0303 health sciences, 030306 microbiology, MESH: Peptidoglycan, Haloactinobacterium, Fatty acid, General Medicine, MESH: Vitamin K 2, MESH: DNA, Bacterial, MESH: Fatty Acids, MESH: RNA, Ribosomal, 16S, MESH: Copper, chemistry, Sister group, MESH: Soil Microbiology, [SDE]Environmental Sciences, Halotolerance, MESH: Actinobacteria
Abstract

In the course of screening the surface soils of ancient copper mines and smelters (East Harz, Germany) an aerobic, non-motile and halotolerant actinobacterium forming small rods or cocci was isolated. The strain designated F300T developed creamy to yellow colonies on tryptone soy agar and grew optimally at 28 °C, pH 7–8 and with 0.5–2 % (m/v) NaCl. Its peptidoglycan was of type A4α l-Lys–l-Glu (A11.54). The menaquinone profile was dominated by MK-8(II, III-H4) and contained minor amounts of MK-8(H2), MK-8(H6) and MK-9(H4). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, mono and diacylated phosphatidylinositol dimannosides, and components that were not fully characterized, including two phospholipids, two glycolipids and an uncharacterized lipid. Major whole-cell sugars were rhamnose and ribose. The fatty acid profile contained mainly iso and anteiso branched fatty acids (anteiso-C15 : 0, iso-C14 : 0) and aldehydes/dimethylacetals (i.e. not fatty acids). Sequence analysis of its genomic DNA and subsequent analysis of the data placed the isolate in the group currently defined by members of the genera Ruania and Haloactinobacterium (family Ruaniaceae , order Micrococcales ) as a sister taxon to the previously described species Haloactinobacterium glacieicola , sharing an average nucleotide identity and average amino acid identity values of 85.3 and 85.7 %, respectively. Genotypic and chemotaxonomic analyses support the view that strain F300T (=DSM 108350T=CIP 111667T) is the type strain of a new genus and new species for which the name Occultella aeris gen. nov., sp. nov. is proposed. Based on revised chemotaxonomic and additional genome based data, it is necessary to discuss and evaluate the results in the light of the classification and nomenclature of members of the family Ruaniaceae , i.e. the genera Haloactinobacterium and Ruania . Consequently, the reclassification of Haloactinobacterium glacieicola as Occultella glacieicola comb. nov. and Haloactinobacterium album as Ruania alba comb. nov., with an emended description of the genus Ruania are proposed.

Published
2021

3. Leaching foams for copper and silver dissolution : a proof of concept of a more environmentally-friendly process for the recovery of critical metals

Author

Mengxue Zhang, Grégory Lefèvre, Alesya Mikhailovskaya, Pierre Trinh, Cécile Monteux, Nadège Pantoustier, Patrick Perrin, Sciences et Ingénierie de la Matière Molle (UMR 7615) (SIMM), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche de Chimie Paris (IRCP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ministère de la Culture (MC), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)

Subjects
MESH: Foams, Materials science, hydrometallurgy, General Chemical Engineering, 0211 other engineering and technologies, chemistry.chemical_element, MESH: Surfactants, metals, 02 engineering and technology, 010501 environmental sciences, recycling, 01 natural sciences, 7. Clean energy, 12. Responsible consumption, hydrometallurgy 2, Environmental Chemistry, [CHIM]Chemical Sciences, Dissolution, 021102 mining & metallurgy, 0105 earth and related environmental sciences, MESH: Metals, Renewable Energy, Sustainability and the Environment, Metallurgy, Foams, General Chemistry, Environmentally friendly, Copper, MESH: Copper, leaching, chemistry, 13. Climate action, Proof of concept, Scientific method, MESH: Bubbles, Leaching (metallurgy)
Abstract

International audience; The recovery of metals from WEEE, Waste from Electrical and Electronic Equipment, is a major challenge to preserve natural resources. Hydrometallurgy, which consists in leaching metals is a promising method but generates large amounts of polluting effluents. In this study we design aqueous leaching foams, composed of 90% v/v of gas and 10% v/v of HCl solution to oxidize and dissolve copper. We take advantage of the oxidizing power of the dioxygen (O2) present in the air bubbles whose fast transfer through the foams enables an efficient oxidation of copper. We then extend the concept of leaching foams to another gas, ozone, to oxidize silver (Ag). We finally show that using an anionic surfactant to complex cupric ions helps improving the dissolution of the metal. These promising results open new recycling routes for metals contained in WEEE, with a lower environmental footprint.

Published
2021

4. Efficacy of Ciprofloxacin and Its Copper Complex against Pseudomonas aeruginosa Biofilms

Author

Frederic Tewes, Hugh D. C. Smyth, Tania F. Bahamondez-Canas, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Molecular Pharmaceutics and Drug Delivery [Austin, TX, USA] (College of Pharmacy), and The University of Texas at Austin

Subjects
[SDV]Life Sciences [q-bio], Antibiotics, Pharmaceutical Science, 02 engineering and technology, medicine.disease_cause, 030226 pharmacology & pharmacy, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, 0302 clinical medicine, Ciprofloxacin, Drug Discovery, chemistry.chemical_classification, MESH: Microbial Sensitivity Tests, Liposome, Pyoverdine, Ecology, copper-based antimicrobials, biofilm infections, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Anti-Bacterial Agents, 3. Good health, MESH: Copper, Drug Combinations, MESH: Pseudomonas aeruginosa, Pseudomonas aeruginosa, 0210 nano-technology, medicine.drug, medicine.drug_class, pulmonary delivery, Virulence, MESH: Biofilms, Microbial Sensitivity Tests, Aquatic Science, Microbiology, 03 medical and health sciences, MESH: Anti-Bacterial Agents, medicine, Humans, MESH: Ciprofloxacin, Ecology, Evolution, Behavior and Systematics, MESH: Drug Combinations, MESH: Humans, Dose-Response Relationship, Drug, Biofilm, biochemical phenomena, metabolism, and nutrition, Enzyme, chemistry, Biofilms, Agronomy and Crop Science, Copper
Abstract

International audience; A limitation of antibiotic treatments for P. aeruginosa (PA) chronic pulmonary infections is the reduced efficacy due to sub-therapeutic concentrations at the infection site and the development of biofilm. A novel approach to sustain ciprofloxacin (CIP) in the lungs after inhalation is to reduce its pulmonary absorption rate by its complexation with copper (CIP-Cu). This study aimed to evaluate the antimicrobial action of cationic CIP-Cu complex in PA biofilms in terms of drug concentration and time. Two PA strains, PA01 and PA14, were grown to form biofilm layers in equilibrium with planktonic cells. Static parameters such as pyoverdine production by planktonic cells, enzymatic activity within biofilms, and biofilm biomass 24 h after the addition of CIP or CIP-Cu were evaluated. Also, the kinetic effects of CIP and CIP-Cu on biofilms were evaluated by bioluminescence kinetics using transgenic strains. No differences were observed between CIP and CIP-Cu in terms of efficacy against biofilms, validating the potential of using this complex to treat PA biofilms. Interestingly, CIP concentrations slightly below the MIC value against planktonic bacteria stimulated both virulence and biofilm PA01 production. These results support the need to accurately achieve high CIP concentration in the lungs, which can be more easily achieved by pulmonary delivery of advanced CIP formulations (CIP-metal complexes or liposomal CIP) instead of the oral administration of free CIP.

Published
2019

5. Structural and electronic determinants of lytic polysaccharide monooxygenase reactivity on polysaccharide substrates

Author

Simmons, T. J., Frandsen, K. E. H., Ciano, L., Tryfona, T., Lenfant, N., Poulsen, J. C., Wilson, L. F. L., Tandrup, T., Tovborg, M., Schnorr, K., Johansen, K. S., Henrissat, B., Walton, P. H., Lo Leggio, L, Dupree, P., Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), UK Biotechnology and Biological Sciences Research Council BB/L000423/1 BB/L021633/1, Danish Council for Strategic Research 12-134923 12-134922, and European Project: 283570,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2011-1,BIOSTRUCT-X(2011)

Subjects
Models, Molecular, MESH: Sordariales, Polysaccharides/chemistry, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Sordariales, MESH: Catalytic Domain, Mixed Function Oxygenases/chemistry, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mixed Function Oxygenases, Substrate Specificity, Polyporaceae, enzyme lytique, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Catalytic Domain, lcsh:Science, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Vegetal Biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Polyporaceae/enzymology, monooxygénase, MESH: Mixed Function Oxygenases, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Copper, glucomannane, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], xyloglucane, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Copper/chemistry, MESH: Fungal Proteins, MESH: Models, Molecular, Fungal Proteins/chemistry, Science, Article, Fungal Proteins, MESH: Polyporaceae, Polysaccharides, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Electron Spin Resonance Spectroscopy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Sordariales/enzymology, carbohydrates (lipids), MESH: Polysaccharides, polysaccharide, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Electron Spin Resonance Spectroscopy, lcsh:Q, MESH: Substrate Specificity, Biologie végétale, Copper
Abstract

Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper-dependent enzymes that oxidatively cleave polysaccharides. Here we present a functional and structural characterization of two closely related AA9-family LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan, mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non-cellulosic oligosaccharides provide insight into the molecular determinants of their specificity. Spectroscopic measurements reveal differences in copper co-ordination upon the binding of xylan and glucans. LsAA9A activity is less sensitive to the reducing agent potential when cleaving xylan, suggesting that distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these data show that AA9 LPMOs can display different apparent substrate specificities dependent upon both productive protein–carbohydrate interactions across a binding surface and also electronic considerations at the copper active site., Copper-dependent lytic polysaccharide monooxygenases (LPMOs) oxidatively cleave polysaccharides. Here the authors present a structure-function characterization of fungal LPMOs, showing that a particular LPMO cleaves xylan using a mechanism that involves an alternative copper coordination geometry.

Published
2017

6. Targeted Shiga toxin–drug conjugates prepared via Cu-free click chemistry

Author

Frédéric Schmidt, Siau-Kun Bai, Vesela Kostova, Estelle Dransart, Michel Azoulay, Ludger Johannes, Jean-Claude Florent, Laura Brulle, Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5)

Subjects
[SDV]Life Sciences [q-bio], MESH: HT29 Cells, Clinical Biochemistry, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Drug Design, Biochemistry, Drug Discovery, MESH: Microscopy, Confocal, Moiety, Cytotoxicity, Drug Carriers, Targeted drug delivery, Microscopy, Confocal, biology, Chemistry, Shiga toxin, 3. Good health, MESH: Copper, MESH: Drug Carriers, MESH: Cell Survival, MESH: Oligopeptides, Click chemistry, Molecular Medicine, Drug carrier, HT29 Cells, Oligopeptides, medicine.drug, Biodistribution, Cell Survival, MESH: Biological Transport, MESH: Shiga Toxin, Antineoplastic Agents, Antibodies, MESH: Doxorubicin, medicine, [CHIM]Chemical Sciences, Humans, Doxorubicin, MESH: Click Chemistry, Molecular Biology, MESH: Humans, MESH: Antibodies, Organic Chemistry, Auristatin, Biological Transport, Copper-free click, Combinatorial chemistry, Drug Design, MESH: HeLa Cells, biology.protein, MESH: Antineoplastic Agents, Click Chemistry, Copper, HeLa Cells
Abstract

International audience; The main drawback of the anticancer chemotherapy consists in the lack of drug selectivity causing severe side effects. The targeted drug delivery appears to be a very promising strategy for controlling the biodistribution of the cytotoxic agent only on malignant tissues by linking it to tumor-targeting moiety. Here we exploit the natural characteristics of Shiga toxin B sub-unit (STxB) as targeting carrier on Gb3-positive cancer cells. Two cytotoxic conjugates STxB-doxorubicin (STxB-Doxo) and STxB-monomethyl auristatin F (STxB-MMAF) were synthesised using copper-free 'click' chemistry. Both conjugates were obtained in very high yield and demonstrated strong tumor inhibition activity in a nanomolar range on Gb3-positive cells.

Published
2015

7. Combined effect of copper and hydrodynamic conditions on Myriophyllum alterniflorum biomarkers

Author

Patrice Fondanèche, Véronique Kazpard, Maha Krayem, Pascal Labrousse, Véronique Deluchat, Philippe Hourdin, Florence Lecavelier Des Etangs, Christian Moesch, Groupement de Recherche Eau, Sol, Environnement (GRESE), Université de Limoges (UNILIM), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Lebanese University [Beirut] (LU), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)

Subjects
0106 biological sciences, Chlorophyll, Health, Toxicology and Mutagenesis, MESH: Plant Shoots, MESH: Plant Roots, MESH: Water Quality, 010501 environmental sciences, 01 natural sciences, MESH: Chlorophyll A, Plant Roots, chemistry.chemical_compound, Water Quality, Biomonitoring, Osmotic pressure, Photosynthesis, MESH: Photosynthesis, biology, General Medicine, Pollution, 6. Clean water, MESH: Copper, Environmental chemistry, Shoot, MESH: Hydrogen Peroxide, MESH: Chlorophyll, MESH: Environmental Monitoring, Plant Shoots, Environmental Monitoring, Chlorophyll a, Environmental Engineering, Cell Respiration, chemistry.chemical_element, Myriophyllum alterniflorum, MESH: Hydrodynamics, Aquatic plant, Environmental Chemistry, 0105 earth and related environmental sciences, Chlorophyll A, Public Health, Environmental and Occupational Health, General Chemistry, Hydrogen Peroxide, biology.organism_classification, Copper, Hydrodynamic conditions, chemistry, Oxidative stress, MESH: Biomarkers, Hydrodynamics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Cell Respiration, Biomarkers, 010606 plant biology & botany
Abstract

The aim of this study is to determine the combined effect of copper and hydrodynamic conditions on the response of certain biomarkers of an aquatic macrophyte, namely Myriophyllum alterniflorum . Watermilfoil biomarkers are monitored in a synthetic medium enriched or not with copper (100 μg.L −1 ) for 21 days in aquarium systems (150 L), under three hydrodynamic conditions: laminar, turbulent, and calm. The studied biomarkers are: respiratory and photosynthetic activities; concentrations of chlorophyll a , b and carotenoids; osmotic potential; hydrogen peroxide content; and growth. In addition, Cu contents in water and in Myriophyllum alterniflorum (roots and shoots) are investigated. The hydrodynamic conditions only affect watermilfoil morphology. Copper accumulates less in turbulent zones; moreover, it is more likely to accumulate in shoots than in roots, except within the calm zone. Cu leads to: i) a significant increase in H 2 O 2 content, ii) a decrease in root growth, pigment content, osmotic potential, photosynthesis and respiration rates, and iii) an inhibition of shoot branching. Differential effects are also observed between younger and older parts, thus indicating the benefit of considering these two plant parts separately in water quality biomonitoring.

Published
2017

8. Structural and Electronic Snapshots during the Transition from a Cu(II) to Cu(I) Metal Center of a Lytic Polysaccharide Monooxygenase by X-ray Photoreduction

Author

Jerry Ståhlberg, Gustav Vaaje-Kolstad, Antoine Royant, Gregg T. Beckham, Daniel Lundberg, Seonah Kim, Majid Hadadd Momeni, Vincent G. H. Eijsink, Mats Sandgren, Takuya Ishida, Miao Wu, Mikael Gudmundsson, Department of Physics, Stockholm University, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), University of Luebeck, Biotechnology and Food Science (Department of Chemistry), Center for Molecular Microbiology, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
inorganic chemicals, Models, Molecular, MESH: Oxidation-Reduction, MESH: Databases, Protein, MESH: Enterococcus faecalis, Inorganic chemistry, MESH: Catalytic Domain, Electrons, Crystal structure, Biochemistry, Mixed Function Oxygenases, Metal, MESH: X-Rays, Polysaccharides, Oxidation state, Catalytic Domain, Enterococcus faecalis, Molecule, Databases, Protein, Molecular Biology, MESH: Electrons, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Chemistry, X-Rays, Active site, Cell Biology, MESH: Mixed Function Oxygenases, Photochemical Processes, Oxygen, MESH: Copper, Crystallography, Trigonal bipyramidal molecular geometry, MESH: Polysaccharides, visual_art, X-ray crystallography, Enzymology, biology.protein, visual_art.visual_art_medium, Quantum Theory, MESH: Photochemical Processes, Oxidation-Reduction, MESH: Quantum Theory, Copper, MESH: Oxygen, MESH: Models, Molecular
Abstract

International audience; Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of enzymes that employ a copper-mediated, oxidative mechanism to cleave glycosidic bonds. The LPMO catalytic mechanism likely requires that molecular oxygen first binds to Cu(I), but the oxidation state in many reported LPMO structures is ambiguous, and the changes in the LPMO active site required to accommodate both oxidation states of copper have not been fully elucidated. Here, a diffraction data collection strategy minimizing the deposited x-ray dose was used to solve the crystal structure of a chitin-specific LPMO from Enterococcus faecalis (EfaCBM33A) in the Cu(II)-bound form. Subsequently, the crystalline protein was photoreduced in the x-ray beam, which revealed structural changes associated with the conversion from the initial Cu(II)-oxidized form with two coordinated water molecules, which adopts a trigonal bipyramidal geometry, to a reduced Cu(I) form in a T-shaped geometry with no coordinated water molecules. A comprehensive survey of Cu(II) and Cu(I) structures in the Cambridge Structural Database unambiguously shows that the geometries observed in the least and most reduced structures reflect binding of Cu(II) and Cu(I), respectively. Quantum mechanical calculations of the oxidized and reduced active sites reveal little change in the electronic structure of the active site measured by the active site partial charges. Together with a previous theoretical investigation of a fungal LPMO, this suggests significant functional plasticity in LPMO active sites. Overall, this study provides molecular snapshots along the reduction process to activate the LPMO catalytic machinery and provides a general method for solving LPMO structures in both copper oxidation states.

Published
2014

9. Antioxidant, metal-binding and DNA-damaging properties of flavonolignans: A joint experimental and computational highlight based on 7-O-galloylsilybin

Author

Veronika Nezhodová, Vladimír Křen, Patrick Trouillas, Jan Hrbac, Jitka Ulrichová, Thomas Desmier, Martina Zatloukalová, Jan Vacek, Martin Kubala, Centre of Biocatalysis and Biotransformation, Institute of Microbiology, Czech Academy of Sciences [Prague] (CAS), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Marquet, Pierre

Subjects
Antioxidant, DNA damage, DPPH, Stereochemistry, medicine.medical_treatment, Molecular Dynamics Simulation, 010402 general chemistry, Toxicology, 01 natural sciences, Antioxidants, Metal, Flavonolignans, chemistry.chemical_compound, Picrates, MESH: Spectrophotometry, Ultraviolet, medicine, Flavonolignan, Moiety, MESH: Molecular Dynamics Simulation, MESH: DNA Damage, MESH: Picrates, 010405 organic chemistry, Biphenyl Compounds, MESH: Antioxidants, Electrochemical Techniques, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Electrochemical Techniques, 0104 chemical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Copper, MESH: Luminescent Measurements, chemistry, Polyphenol, visual_art, Luminescent Measurements, visual_art.visual_art_medium, Spectrophotometry, Ultraviolet, Copper, MESH: Biphenyl Compounds, DNA Damage, Silymarin, MESH: Silymarin
Abstract

International audience; Besides the well-known chemoprotective effects of polyphenols, their prooxidant activities via interactions with biomacromolecules as DNA and proteins are of the utmost importance. Current research focuses not only on natural polyphenols but also on synthetically prepared analogs with promising biological activities. In the present study, the antioxidant and prooxidant properties of a semi-synthetic flavonolignan 7-O-galloylsilybin (7-GSB) are described. The presence of the galloyl moiety significantly enhances the antioxidant capacity of 7-GSB compared to that of silybin (SB). These findings were supported by electrochemistry, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, total antioxidant capacity (CL-TAC) and DFT (density functional theory) calculations. A three-step oxidation mechanism of 7-GSB is proposed at pH 7.4, in which the galloyl moiety is first oxidized at Ep,1=+0.20V (vs. Ag/AgCl3M KCl) followed by oxidation of the 20-OH (Ep,2=+0.55V) and most probably 5-OH (Ep,3=+0.95V) group of SB moiety. The molecular orbital analysis and the calculation of O-H bond dissociation enthalpies (BDE) fully rationalize the electrooxidation processes. The metal (Cu(2+)) complexation of 7-GSB was studied, which appeared to involve both the galloyl moiety and the 5-OH group. The prooxidant effects of the metal-complexes were then studied according to their capacity to oxidatively induce DNA modification and cleavage. These results paved the way towards the conclusion that 7-O-galloyl substitution to SB concomitantly (i) enhances antioxidant (ROS scavenging) capacity and (ii) decreases prooxidant effect/DNA damage after Cu complexation. This multidisciplinary approach provides a comprehensive mechanistic picture of the antioxidant vs. metal-induced prooxidant effects of flavonolignans at the molecular level, under ex vivo conditions.

Published
2013

10. Adaptation of genetically monomorphic bacteria: evolution of copper resistance through multiple horizontal gene transfers of complex and versatile mobile genetic elements

Author

Aude Chabirand, Christian Vernière, Pierre Lefeuvre, Olivier Pruvost, Claudine Boyer, Pierre Grygiel, Damien Richard, Virginie Ravigné, Adrien Rieux, Marie Annabelle Terville, Isabelle Robène, B.I. Canteros, Stéphanie Javegny, Benoit Facon, Karine Boyer, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut National de la Recherche Agronomique (INRA), Instituto Nacional de Tecnología Agropecuaria (INTA), Biologie et Génétique des Interactions Plante-Parasite (UMR BGPI), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), European Regional Development Fund (ERDF), European Agricultural Fund for Rural Development (EAFRD), Conseil Departemental de la Reunion, Region Reunion, Etat francais, French Agropolis Foundation (Labex Agro - Montpellier, E-SPACE) : 1504-004, ANSES, CIRAD, Département Systèmes Biologiques (Cirad-BIOS), 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), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), The European Regional Development Fund (ERDF) and European Agricultural Fund for Rural Development (EAFRD), Conseil Departemental de la Reunion, Region Reunion, Etat francais, the French Agropolis Foundation (Labex Agro - Montpellier, E-SPACE project number 1504-004), ANSES and CIRAD provided financial support., ANR-10-LABX-0001,AGRO,Agricultural Sciences for sustainable Development(2010), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)

Subjects
0301 basic medicine, Citrus, heavy metal resistance, Xanthomonas campestris citri, Xanthomonas citri, Plasmid, Genetics, biology, Adaptation, Physiological, Épidémiologie, MESH: Copper, Stenotrophomonas, PCR, Organisme génétiquement modifié, Cuivre, Citrus canker, mobile DNA, Martinique, MESH: Interspersed Repetitive Sequences, résistance aux maladies, DNA, Bacterial, Séquence nucléotidique, Xanthomonas, Gene Transfer, Horizontal, Genotype, Argentina, Bacterial genome size, MESH: Xanthomonas, 03 medical and health sciences, stomatognathic system, plasmid, MESH: Drug Resistance, Bacterial, Drug Resistance, Bacterial, protection des plantes, contemporary adaptation, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Adaptation, Ecology, Evolution, Behavior and Systematics, H20 - Maladies des plantes, Plant Diseases, Résistance aux pesticides, amélioration génétique, Résistance aux produits chimiques, Xanthomonadaceae, Biologie moléculaire, Microsatellite, biology.organism_classification, Interspersed Repetitive Sequences, resistance to diseases, 030104 developmental biology, Genetics, Population, Gène, Genes, Bacterial, Évaluation, U30 - Méthodes de recherche, Mobile genetic elements, Reunion, Copper, crop protection, Microsatellite Repeats
Abstract

Copper-based compounds are widely used in integrated pest management (1PM) programs aiming at controlling agriculturally important plant bacterial pathogens and the latter have adapted in response to this selective pressure. Copper resistance of Xanthomonas citri pv. citri (Xcc), a major citrus pathogen worldwide causing Asialie citrus canker, was first observed in Argentina two decades ago and subsequently reported as a copLAB-based, plasmid-encoded system. The emergence of resistant strains has since been reported in Réunion (South West lndian Ocean) and Martinique (Eastern Caribbean Sea). Disease severity was found markedly increased in groves established with susceptible cultivars and infected with copper-resistant Xcc. Using tandem repeat-based genotyping and copLAB PCR, we demonstrated that the genetic structure of the copperresistant strains from these three regions was made up of two distant clusters and varied for the detection of copLAB amplicons. ln order to investigate this pattern more closely, we sequenced six copper-resistant Xcc strains from Argentina, Martinique and Réunion, together with reference copper-resistant Xanthomonas and Stenotrophomonas strains using long-read sequencing technology. Genes involved in copper resistance were found to be strain-dependent with the nove! identification in Xcc of copABCD and a eus heavy metal efflux resistance-nodulation-division system. The genes providing the adaptive trait were part of a mobile genetic element similar to Tn3-like transposons and included in a conjugative plasmid. The mining of ail bacterial genomes available from public databases suggested that the mobile elements containing copper resistance genes and their plasmid environments were primarily detected in the Xanthomonadaceae family.

Published
2016

11. Molecular drug design, synthesis and crystal structure determination of CuII–SnIV heterobimetallic core: DNA binding and cleavage studies

Author

Mohd Afzal, Loïc Toupet, Shazia Parveen, Taibi Ben Hadda, Farukh Arjmand, Faculté des sciences [Oujda], Université Mohammed Premier [Oujda], Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Biotechnology, New Delhi (SchemeNo.BT/PR9205/Med/30/13/2007), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, Intercalation (chemistry), Crystal structure, MESH: Drug Design, Crystallography, X-Ray, 01 natural sciences, chemistry.chemical_compound, Coordination Complexes, MESH: Coordination Complexes, Topo I inhibition activity, Drug Discovery, MESH: Phenanthrolines, MESH: Animals, MESH: DNA Cleavage, MESH: Tin, chemistry.chemical_classification, biology, MESH: DNA, General Medicine, Ligand (biochemistry), [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Copper, MESH: Cattle, MESH: Topoisomerase I Inhibitors, MESH: Nucleic Acid Conformation, DNA Topoisomerases, Type I, CuII-SnIV phen complex, CT DNA binding, Molecular docking, Pharmacophore, MESH: Models, Molecular, Phenanthrolines, pBR322 DNA cleavage, Stereochemistry, 010402 general chemistry, Cleavage (embryo), Animals, Humans, DNA Cleavage, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Pharmacology, Nuclease, DNA ligase, MESH: Humans, 010405 organic chemistry, Organic Chemistry, DNA, T4 DNA ligase assay, MESH: Crystallography, X-Ray, 0104 chemical sciences, chemistry, Tin, Drug Design, biology.protein, Nucleic Acid Conformation, Cattle, Topoisomerase I Inhibitors, MESH: DNA Topoisomerases, Type I, Copper
Abstract

International audience; A novel heterobimetallic Cu(II)-Sn(IV) complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 μM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies.

Published
2012

12. Interplay between glutathione, Atx1 and copper: X-ray absorption spectroscopy determination of Cu(I) environment in an Atx1 dimer

Author

Christophe Den Auwer, Michel Ferrand, Elisabeth Mintz, Serge Crouzy, Roger Miras, Clara Fillaux, David Poger, Pascale Delangle, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Chimie des Procédés de Séparation (SCPS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Reconnaissance Ionique et Chimie de Coordination (RICC), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Models, Molecular, MESH: Ions, Coordination sphere, MESH: Biological Transport, Dimer, Inorganic chemistry, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Biochemistry, Ion, Inorganic Chemistry, MESH: Cation Transport Proteins, 03 medical and health sciences, chemistry.chemical_compound, Molecule, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cation Transport Proteins, 030304 developmental biology, Ions, MESH: Glutathione, 0303 health sciences, X-ray absorption spectroscopy, MESH: Protein Multimerization, Spectrometry, X-Ray Emission, Biological Transport, MESH: Spectrometry, X-Ray Emission, Glutathione, Sulfur, Copper, 3. Good health, 0104 chemical sciences, MESH: Copper, Crystallography, chemistry, Protein Multimerization, MESH: Molecular Chaperones, Absorption (chemistry), MESH: Models, Molecular, Molecular Chaperones
Abstract

X-ray absorption techniques have been used to characterise the primary coordination sphere of Cu(I) bound to glutathionate (GS−), to Atx1 and in Cu 2 I (GS−)2(Atx1)2, a complex recently proposed as the major form of Atx1 in the cytosol. In each complex, Cu(I) was shown to be triply coordinated. When only glutathione is provided, each Cu(I) is triply coordinated by sulphur atoms in the binuclear complex CuI 2(GS−)5, involving bridging and terminal thiolates. In the presence of Atx1 and excess of glutathione, under conditions where CuI 2(GS−)2(Atx1)2 is formed, each Cu(I) is triply coordinated by sulphur atoms. Given these constraints, there are two different ways for Cu(I) to bridge the Atx1 dimer: either both Cu(I) ions contribute to bridging the dimer, or only one Cu(I) ion is responsible for bridging, the other one being coordinated to two glutathione molecules. These two models are discussed as regards Cu(I) transfer to Ccc2a.

Published
2008

13. The strong induction of metallothionein gene following cadmium exposure transiently affects the expression of many genes in Eisenia fetida: A trade-off mechanism?

Author

Sébastien Lemière, R. Leroux, F. Brulle, Alain Leprêtre, Guillaume Mitta, Franck Vandenbulcke, Laboratoire d'Ecologie Numérique et d'Ecotoxicologie, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Parasitologie fonctionnelle et évolutive [2003-2006] (PFE), Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique ( CNRS ), Parasitologie fonctionnelle et évolutive ( PFE ), Université de Perpignan Via Domitia ( UPVD ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée ( DAPNIA ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), and Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : RNA, Messenger, Physiology, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Toxicology, 01 natural sciences, Biochemistry, MESH : Soil Pollutants, Soil Pollutants, Metallothionein, MESH: Animals, MESH : Copper, MESH : Cadmium, Regulation of gene expression, 0303 health sciences, MESH : Gene Expression Regulation, Effector, MESH: Cyclophilin A, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Oligochaeta, General Medicine, MESH: Gene Expression Regulation, MESH: Copper, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH : Oligochaeta, Cyclophilin A, Cadmium, Eisenia fetida, MESH: Cadmium, MESH : Cyclophilin A, Biology, Superoxide dismutase, MESH: Gene Expression Profiling, 03 medical and health sciences, Heat shock protein, Animals, RNA, Messenger, Oligochaeta, Protein kinase C, MESH: RNA, Messenger, 030304 developmental biology, 0105 earth and related environmental sciences, MESH: Soil Pollutants, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Metallothionein, MESH: Biological Markers, Cell Biology, biology.organism_classification, MESH : Metallothionein, MESH : Biological Markers, Gene expression profiling, Gene Expression Regulation, 13. Climate action, biology.protein, MESH : Animals, Biomarkers, Copper
Abstract

Metal pollution causes disturbances at various levels of biological organization in most species. Important physiological functions could be affected in the exposed individuals and among the main physiological functions, immunity may provide one (or more) effector(s) whose expression can be directly affected by a metal exposure in various macroinvertebrates. Protein expressions were studied in order to test them as molecular biomarkers of metal exposure in Eisenia fetida. Selected effectors were calmodulin, heat shock proteins, superoxide dismutase, catalase, metallothionein, beta-adrenergic receptor kinase, pyruvate carboxylase, transcriptionally controlled tumor protein, protein kinase C, ubiquitin and cyclophilin-A. The level of expression of each gene was analysed in whole organism following exposures to cadmium in soil using real-time PCR. Metallothionein, transcriptionally controlled tumor protein and cyclophilin-A expression were also measured following copper exposures in soil because these genes seemed to be sensitive to copper. This work enabled to distinguish metallothionein and cyclophilin-A among the 15 selected effectors. A strong decrease of the number of transcripts was also detected for most effectors soon after the exposure to cadmium suggesting that a trade-off mechanism occurs.

Published
2007

14. Copper trafficking to the mitochondrion and assembly of copper metalloenzymes

Author

Paul A. Cobine, Dennis R. Winge, Fabien Pierrel, University of Utah, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Models, Molecular, Protein Conformation, MESH: Mitochondria, Mitochondrial intermembrane space, MESH: Biological Transport, chemistry.chemical_element, macromolecular substances, Mitochondrion, Cytochrome oxidase, Electron Transport Complex IV, Superoxide dismutase, 03 medical and health sciences, MESH: Protein Conformation, MESH: Electron Transport Complex IV, COX17, Cytochrome c oxidase, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Metallochaperone, 030302 biochemistry & molecular biology, nutritional and metabolic diseases, Biological Transport, Cell Biology, Copper, Mitochondria, MESH: Copper, Biochemistry, Cytoplasm, Mitochondrial matrix, Biophysics, biology.protein, MESH: Models, Molecular
Abstract

International audience; Copper is required within the mitochondrion for the function of two metalloenzymes, cytochrome c oxidase (CcO) and superoxide dismutase (Sod1). Copper metallation of these two enzymes occurs within the mitochondrial intermembrane space and is mediated by metallochaperone proteins. Cox17 is a key copper donor to two accessory proteins, Sco1 and Cox11, to form the two copper centers in the mature CcO complex. Ccs1 is the necessary metallochaperone for the copper metallation of Sod1 in the IMS as well as within the cytoplasm where the bulk of Sod1 resides. Copper ions used in the metallation of CcO and Sod1 appear to be provided by a novel copper pool within the mitochondrial matrix. This review documents copper ion shuttling within the mitochondrion and the proteins that mediate assembly of active CcO and Sod1.

Published
2006

15. Characterization of a UDP-N-acetyl-<scp>D</scp>-galactosamine:polypeptide N-acetylgalactosaminyltransferase with an unusual lectin domain from the platyhelminth parasite Echinococcus granulosus

Author

Teresa Freire, Cora Chalar, Carlos Robello, Pedro M. Alzari, Cecilia Fernández, Eduardo Osinaga, Rick M. Maizels, Facultad de Medicina [Universidad de la Republica, Uruguay], Universidad de la República [Montevideo] (UCUR), University of Edinburgh, Facultad de Ciencias (UDELAR), Biochimie Structurale, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], This work was supported in part by Comisión Sectorial de Investigación Científica (Uruguay) and the ECOS France–Uruguay Programme. C.F. was awarded a Travel Research Fellowship from the Wellcome Trust., Universidad de la República [Montevideo] (UDELAR), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Sequence Analysis, DNA, MESH: Hydrogen-Ion Concentration, MESH: Helminth Proteins, Helminth genetics, MESH: Amino Acid Sequence, MESH: DNA, Helminth, MESH: Echinococcus granulosus, Biochemistry, Substrate Specificity, MESH: Protein Structure, Tertiary, chemistry.chemical_compound, MESH: Lectins, Protein structure, MESH: Chlorocebus aethiops, Lectins, Chlorocebus aethiops, MESH: Cattle Diseases, MESH: Animals, Cloning, Molecular, Echinococcus granulosus, Peptide sequence, O-glycosylation, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, MESH: Peptides, 030302 biochemistry & molecular biology, Helminth Proteins, DNA, Helminth, Hydrogen-Ion Concentration, MESH: COS Cells, MESH: Copper, MESH: Cattle, Transmembrane domain, COS Cells, N-Acetylgalactosaminyltransferases, Research Article, DNA, Complementary, UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase, Glycosylation, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Molecular Sequence Data, Polypeptide N-acetylgalactosaminyltransferase, Cattle Diseases, MESH: Manganese, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: N-Acetylgalactosaminyltransferases, helminth parasite, Cell Line, MESH: Echinococcosis, 03 medical and health sciences, Echinococcosis, parasitic diseases, [CHIM.CRIS]Chemical Sciences/Cristallography, Animals, MESH: Cloning, Molecular, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Molecular Biology, 030304 developmental biology, Manganese, MESH: Molecular Sequence Data, Lectin, Sequence Analysis, DNA, MESH: DNA, Complementary, Cell Biology, biology.organism_classification, Protein Structure, Tertiary, MESH: Cell Line, chemistry, biology.protein, Cattle, MESH: Substrate Specificity, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Peptides, Copper
Abstract

International audience; As part of a general project aimed at elucidating the initiation of mucin-type O-glycosylation in helminth parasites, we have characterized a novel ppGalNAc-T (UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase) from the cestode Echinococcus granulosus (Eg-ppGalNAc-T1). A full-length cDNA was isolated from a library of the tissue-dwelling larval stage of the parasite, and found to code for a 654-amino-acid protein containing all the structural features of ppGalNAc-Ts. Functional characterization of a recombinant protein lacking the transmembrane domain showed maximal activity at 28 degrees C, in the range 6.5-7.5 pH units and in the presence of Cu2+. In addition, it transferred GalNAc to a broad range of substrate peptides, derived from human mucins and O-glycosylated parasite proteins, including acceptors containing only serine or only threonine residues. Interestingly, the C-terminal region of Eg-ppGalNAc-T1 bears a highly unusual lectin domain, considerably longer than the one from other members of the family, and including only one of the three ricin B repeats generally present in ppGalNAc-Ts. Furthermore, a search for conserved domains within the protein C-terminus identified a fragment showing similarity to a recently defined domain, specialized in the binding of organic phosphates (CYTH). The role of the lectin domain in the determination of the substrate specificity of these enzymes suggests that Eg-ppGalNAc-T1 would be involved in the glycosylation of a special type of substrate. Analysis of the tissue distribution by in situ hybridization and immunohistochemistry revealed that this transferase is expressed in the hydatid cyst wall and the subtegumental region of larval worms. Therefore it could participate in the biosynthesis of O-glycosylated parasite proteins exposed at the interface between E. granulosus and its hosts.

Published
2004

16. Transcriptomic and metabolomic analysis of copper stress acclimation in Ectocarpus siliculosus highlights signaling and tolerance mechanisms in brown algae

Author

Sophie Goulitquer, Andrés Ritter, Juan A. Correa, Thierry Tonon, Catherine Boyen, Simon M. Dittami, Philippe Potin, Departamento de Ecología Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile (UC), Végétaux marins et biomolécules, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-GOEMAR-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Departamento de Ecologia, Departamento de Ecología, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile, Departamento de Ecología, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile-Departamento de Ecología, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile, Center of applied ecology & sustainability (CAPES), Facultad de ciencias biologicas [Santiago], Pontificia Universidad Católica de Chile (UC)-Pontificia Universidad Católica de Chile (UC), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Défense des algues, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Station biologique de Roscoff [Roscoff] (SBR), MetaboMER, Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR)

Subjects
MESH: Signal Transduction, MESH: Algal Proteins, MESH: Amino Acids, Acclimatization, Molecular Networks (q-bio.MN), [SDV]Life Sciences [q-bio], Primary metabolism, Plant Science, medicine.disease_cause, MESH: Down-Regulation, MESH: Least-Squares Analysis, MESH: Up-Regulation, Cluster Analysis, Quantitative Biology - Molecular Networks, Amino Acids, Photosynthesis, MESH: Metabolomics, MESH: Phylogeny, MESH: Stress, Physiological, Chromatography, High Pressure Liquid, Phylogeny, MESH: Photosynthesis, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Abiotic component, Copper stress response, MESH: Oxidative Stress, Ectocarpus siliculosus, Fatty Acids, Discriminant Analysis, MESH: Phaeophyta, Up-Regulation, MESH: Fatty Acids, Cell biology, MESH: Copper, Heavy metal, ABC transporters, Metabolome, Metabolic Networks and Pathways, MESH: Metabolome, Research Article, Signal Transduction, MESH: Oxylipins, Brown algae, Down-Regulation, MESH: Acclimatization, Biology, Phaeophyta, Gas Chromatography-Mass Spectrometry, MESH: Gene Expression Profiling, Metabolomics, Stress, Physiological, Botany, medicine, Humans, Quantitative Biology - Genomics, Oxylipins, 14. Life underwater, Least-Squares Analysis, MESH: Chromatography, High Pressure Liquid, Genomics (q-bio.GN), MESH: Humans, Abiotic stress, Gene Expression Profiling, MESH: Transcriptome, Algal Proteins, MESH: Discriminant Analysis, Oxylipin, biology.organism_classification, MESH: Cluster Analysis, MESH: Gas Chromatography-Mass Spectrometry, Oxidative Stress, Multicellular organism, MESH: Metabolic Networks and Pathways, FOS: Biological sciences, Transcriptome, Copper, Oxidative stress
Abstract

International audience; Background: Brown algae are sessile macro-organisms of great ecological relevance in coastal ecosystems. They evolved independently from land plants and other multicellular lineages, and therefore hold several original ontogenic and metabolic features. Most brown algae grow along the coastal zone where they face frequent environmental changes, including exposure to toxic levels of heavy metals such as copper (Cu). Results: We carried out large-scale transcriptomic and metabolomic analyses to decipher the short-term acclimation of the brown algal model E. siliculosus to Cu stress, and compared these data to results known for other abiotic stressors. This comparison demonstrates that Cu induces oxidative stress in E. siliculosus as illustrated by the transcriptomic overlap between Cu and H 2 O 2 treatments. The common response to Cu and H 2 O 2 consisted in the activation of the oxylipin and the repression of inositol signaling pathways, together with the regulation of genes coding for several transcription-associated proteins. Concomitantly, Cu stress specifically activated a set of genes coding for orthologs of ABC transporters, a P 1B-type ATPase, ROS detoxification systems such as a vanadium-dependent bromoperoxidase, and induced an increase of free fatty acid contents. Finally we observed, as a common abiotic stress mechanism, the activation of autophagic processes on one hand and the repression of genes involved in nitrogen assimilation on the other hand. Conclusions: Comparisons with data from green plants indicate that some processes involved in Cu and oxidative stress response are conserved across these two distant lineages. At the same time the high number of yet uncharacterized brown alga-specific genes induced in response to copper stress underlines the potential to discover new components and molecular interactions unique to these organisms. Of particular interest for future research is the potential cross-talk between reactive oxygen species (ROS)-, myo-inositol-, and oxylipin signaling.

Published
2014

17. Joint-action of antifouling substances in copper-free paints

Author

Karine Vallée-Réhel, David Carteau, Isabelle Linossier, Maxime Delbury, Fabienne Faÿ, Laboratoire de Biotechnologie et Chimie Marines (LBCM), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Non ionic, Biofouling, chemistry.chemical_element, Polysorbates, 02 engineering and technology, MESH: Paint, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, Colloid and Surface Chemistry, Paint, Zinc peroxide, Physical and Theoretical Chemistry, Hydrogen peroxide, 0303 health sciences, 030306 microbiology, Chlorhexidine, MESH: Polysorbates, Eukaryota, Surfaces and Interfaces, General Medicine, Hydrogen Peroxide, MESH: Biofouling, 021001 nanoscience & nanotechnology, Copper, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Joint action, MESH: Chlorhexidine, MESH: Copper, MESH: Eukaryota, chemistry, Chemical engineering, Tributyltin, MESH: Hydrogen Peroxide, 0210 nano-technology, Biotechnology
Abstract

International audience; Due to the environmentally harmful impact of tributyltin self-polishing paints, there is a critical need of more ecological alternatives. The aim of the present work is to study the joint-action of three molecules chosen in order to combine the two modes of prevention: chemical and physical repelling of biofouling. This "hybrid" system is principally dedicated to disturb durable settlement of microfouling. Each component was chosen according to its specific properties: chlorhexidine is a bisdiguanide antiseptic with antibacterial activity, zinc peroxide is an inorganic precursor of high instable entities which react with seawater to create hydrogen peroxide, Tween 85 is a non ionic surfactant disturbing interactions between colonizing organisms and surface. Obtained results highlighted the interest on mixing such molecules to get additive action on antifouling efficiency.

Published
2012

18. Physiological relevance and contribution to metal balance of specific and non-specific Metallothionein isoforms in the garden snail, Cantareus aspersus

Author

Reinhard Dallinger, Sílvia Pérez-Rafael, Annette de Vaufleury, Martina Höckner, Karin Stefanon, Òscar Palacios, Sílvia Atrian, Freddy Monteiro, Mercè Capdevila, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut für Zoologie, Universität Innsbruck [Innsbruck], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
MESH : Molecular Sequence Data, Transcription, Genetic, [ SDV.TOX.ECO ] Life Sciences [q-bio]/Toxicology/Ecotoxicology, MESH: Amino Acid Sequence, MESH: Protein Isoforms, 010501 environmental sciences, 01 natural sciences, Mass Spectrometry, MESH: Recombinant Proteins, Transcription (biology), MESH: Helix (Snails), Metallothionein, Protein Isoforms, MESH: Animals, MESH : Copper, Peptide sequence, Chromatography, High Pressure Liquid, MESH : Cadmium, 0303 health sciences, Cadmium, biology, Ecology, MESH : Amino Acid Sequence, MESH : Sequence Alignment, Metals and Alloys, Recombinant Proteins, MESH: Copper, Biochemistry, MESH : Helix (Snails), [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, General Agricultural and Biological Sciences, Gene isoform, MESH : Recombinant Proteins, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Cadmium, chemistry.chemical_element, Sequence alignment, Pulmonata, General Biochemistry, Genetics and Molecular Biology, Biomaterials, 03 medical and health sciences, MESH : Chromatography, High Pressure Liquid, MESH : Mass Spectrometry, Animals, Amino Acid Sequence, MESH: Chromatography, High Pressure Liquid, Gene, 030304 developmental biology, 0105 earth and related environmental sciences, MESH: Mass Spectrometry, MESH: Molecular Sequence Data, MESH: Transcription, Genetic, Helix, Snails, MESH: Metallothionein, MESH : Transcription, Genetic, MESH : Protein Isoforms, biology.organism_classification, MESH : Metallothionein, chemistry, MESH : Animals, Sequence Alignment, Copper
Abstract

International audience; Variable environmental availability of metal ions represents a constant challenge for most organisms, so that during evolution, they have optimised physiological and molecular mechanisms to cope with this particular requirement. Metallothioneins (MTs) are proteins that play a major role in metal homeostasis and as a reservoir. The MT gene/protein systems of terrestrial helicid snails are an invaluable model for the study of metal-binding features and MT isoform-specific functionality of these proteins. In the present study, we characterised three paralogous MT isogenes and their expressed products in the escargot (Cantareus aspersus). The metal-dependent transcriptional activation of the three isogenes was assessed using quantitative Real Time PCR. The metal-binding capacities of the three isoforms were studied by characterising the purified native complexes. All the data were analysed in relation to the trace element status of the animals after metal feeding. Two of the three C. aspersus MT (CaMT) isoforms appeared to be metal-specific, (CaCdMT and CaCuMT, for cadmium and copper respectively). A third isoform (CaCd/CuMT) was non-specific, since it was natively recovered as a mixed Cd/Cu complex. A specific role in Cd detoxification for CaCdMT was revealed, with a 80-90% contribution to the Cd balance in snails exposed to this metal. Conclusive data were also obtained for the CaCuMT isoform, which is involved in Cu homeostasis, sharing about 30-50% of the Cu balance of C. aspersus. No apparent metal-related physiological function was found for the third isoform (CaCd/CuMT), so its contribution to the metal balance of the escargot may be, if at all, of only marginal significance, but may enclose a major interest in evolutionary studies.

Published
2011

19. The toxicity redox mechanisms of cadmium alone or together with copper and zinc homeostasis alteration: its redox biomarkers

Author

Alain Favier, Serge M. Candéias, Sylvie Sauvaigo, Yves Nzengue, Thierry Douki, Pascale Guiraud, Walid Rachidi, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Biochimie et Génétique Moléculaire (LBGM), Université de La Réunion (UR), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
MESH: Oxidation-Reduction, Antioxidant, DNA damage, medicine.medical_treatment, MESH: Cadmium, chemistry.chemical_element, medicine.disease_cause, Biochemistry, MESH: Zinc, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Homeostasis, Humans, MESH: Animals, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Cadmium, Reactive oxygen species, MESH: Humans, Copper toxicity, MESH: Biological Markers, Glutathione, medicine.disease, 3. Good health, MESH: Copper, Zinc, chemistry, MESH: Homeostasis, 030220 oncology & carcinogenesis, Zinc toxicity, Toxicity, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Oxidation-Reduction, Biomarkers, Copper
Abstract

International audience; Cadmium (Cd) is a toxic metal and can induce and/or promote diseases in humans (cancer, aging diseases, kidney and bone diseases, etc.). Its toxicity involves many mechanisms including the alteration of copper (Cu) and zinc (Zn) homeostasis leading to reactive oxygen species (ROS) production, either directly or through the inhibition of antioxidant activities. Importantly, ROS can induce oxidative damages in cells. Cadmium, Cu and Zn are also able to induce glutathione (GSH) and metallothioneins (MT) synthesis in a cell-type-dependent manner. As a consequence, the effects induced by these three metals result simultaneously from the inhibition of antioxidant activities and the induction of other factors such as GSH and MT synthesis. MT levels are regulated not only by the p53 protein in a cell-type-dependent manner, or by transcription factors such as metal-responsive transcription factor 1 (MTF-1) and cellular Zn levels but also by cellular GSH level. As described in the literature, DNA damage, GSH and MT levels are sensitive biomarkers used to identify Cd-induced toxicity alone or together with Cu and Zn homeostasis alteration.

Published
2011

20. PtrA is a periplasmic protein involved in Cu tolerance in Pseudomonas aeruginosa

Author

Michel Ragno, Ina Attree, Sylvie Elsen, Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Pathogénie bactérienne et réponses cellulaires, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transcription, Genetic, chemistry.chemical_element, medicine.disease_cause, Microbiology, Type three secretion system, Periplasmic Proteins, 03 medical and health sciences, Bacterial Proteins, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, Molecular Biology, MESH: Bacterial Proteins, 030304 developmental biology, Molecular Biology of Pathogens, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, biology, 030306 microbiology, Pseudomonas aeruginosa, MESH: Transcription, Genetic, Gene Expression Regulation, Bacterial, Periplasmic space, biology.organism_classification, Copper, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Copper, Biochemistry, chemistry, Pseudomonadales, MESH: Pseudomonas aeruginosa, Bacteria, Pseudomonadaceae, MESH: Periplasmic Proteins
Abstract

In this work, we demonstrate that PtrA (U. H. Ha et al., Mol. Microbiol. 54:307–320, 2004) is a periplasmic protein, specifically synthesized in the presence of copper, that is involved in the tolerance of Pseudomonas aeruginosa to copper. Our biochemical and genetic analyses challenge its role in transcriptional inhibition of the type III secretion system.

Published
2011

21. Electrochemical synthesis and characterisation of alternating tripyridyl-dipyrrole molecular strands with multiple nitrogen-based donor-acceptor binding sites

Author

Karène Urgin, Michel Evain, Yann Ferrand, Thierry Delaunay, Alexandra Tabatchnik‐Rebillon, Sylvie Condon, Marine Soulard, Muriel Pipelier, Eric Léonel, Christine Thobie-Gautier, Denis Jacquemin, Christiane Guguen-Guillouzo, Jacques Lebreton, Jean-Yves Le Questel, Eric Renault, Virginie Blot, Rémy Le Guével, Hicham Bakkali, G. T. Manh, Ivan Huc, Brice Kauffmann, Christophe Aube, Didier Dubreuil, Aurélien Planchat, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Male, Pyridines, Ligands, 01 natural sciences, chemistry.chemical_compound, N ligands, MESH: Ligands, MESH: Nitrogen, Zinc bromide, Pyrrole, Molecular Structure, Negishi coupling, MESH: Models, Chemical, MESH: Drug Screening Assays, Antitumor, MESH: Electrochemical Techniques, MESH: Copper, MESH: Pyrroles, Female, Nitrogen, Inorganic chemistry, MESH: Molecular Structure, Antineoplastic Agents, 010402 general chemistry, Electrosynthesis, Catalysis, MESH: Cell Proliferation, Pyridine, Molecule, Humans, Pyrroles, Acetonitrile, Cell Proliferation, Binding Sites, MESH: Humans, 010405 organic chemistry, Organic Chemistry, MESH: Pyridines, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Chemistry, Electrochemical Techniques, Chromophore, MESH: Catalysis, MESH: Male, 0104 chemical sciences, Crystallography, chemistry, Models, Chemical, electrochemistry, MESH: Binding Sites, copper, MESH: Antineoplastic Agents, nitrogen heterocycles, Drug Screening Assays, Antitumor, MESH: Female, ring contraction
Abstract

International audience; Synthesis of alternating pyridine-pyrrole molecular strands composed of two electron-rich pyrrole units (donors) sandwiched between three pyridinic cores (acceptors) is described. The envisioned strategy was a smooth electrosynthesis process involving ring contraction of corresponding tripyridyl-dipyridazine precursors. 2,6-Bis[6-(pyridazin-3-yl)]pyridine ligands 2a-c bearing pyridine residues at the terminal positions were prepared in suitable quantities by a Negishi metal cross-coupling procedure. The yields of heterocyclic coupling between 2-pyridyl zinc bromide reagents 12a-c and 2,6-bis(6-trifluoromethanesulfonylpyridazin-3-yl)pyridine increased from 68 to 95% following introduction of electron-donating methyl groups on the metallated halogenopyridine units. Favorable conditions for preparative electrochemical reduction of tripyridyl-dipyridazines 2b,c were established in THF/acetate buffer (pH 4.6)/acetonitrile to give the targeted 2,6-bis[5-(pyridin-2-yl)pyrrol-2-yl]pyridines 1b and 1c in good yields. The absorption behavior of the donor-acceptor tripyridyl-dipyrrole ligands was evaluated and compared to theoretical calculations. Highly fluorescent properties of these chromophores were found (ν(em)≈2 × 10(4) cm(-1) in MeOH and CH(2)Cl(2)), and both pyrrolic ligands exhibit a remarkable quantum yield in CH(2)Cl(2) (φ(f)=0.10). Structural studies in the solid state established the preferred cis conformation of the dipyrrolic ligands, which adopting a planar arrangement with an embedded molecule of water having a complexation energy exceeding 10 kcal mol(-1). The ability of the tripyridyl-dipyrrole to complex two copper(II) ions in a pentacoordinate square was investigated.

Published
2010

22. Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

Author

R, Bolea, P, Hortells, I, Martín-Burriel, A, Vargas, B, Ryffel, M, Monzón, J J, Badiola, Research Centre for Prion Diseases, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Mice, Transgenic, MESH: Neurons, MESH: Manganese, Apoptosis, Mice, Transgenic, Nerve Tissue Proteins, Pregnancy Proteins, Mice, MESH: Brain, MESH: Diet, MESH: Mice, Inbred C57BL, MESH: Caspase 3, Animals, MESH: Animals, MESH: bcl-2-Associated X Protein, MESH: Nerve Tissue Proteins, MESH: Mice, bcl-2-Associated X Protein, Neurons, Manganese, MESH: Pregnancy Proteins, Caspase 3, MESH: Apoptosis, Brain, Nuclear Proteins, Diet, DNA-Binding Proteins, Mice, Inbred C57BL, MESH: Copper, Disease Models, Animal, MESH: Scrapie, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Disease Models, Animal, MESH: Nuclear Proteins, Copper, Scrapie
Abstract

International audience; AIMS: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains. The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. METHODS: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (-Cu), loaded manganese (+Mn), depleted copper/loaded manganese (-Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. RESULTS: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the -Cu, -Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death. CONCLUSIONS: With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity.

Published
2010

23. Copper-free click chemistry for highly luminescent quantum dot conjugates: application to in vivo metabolic imaging

Author

David Bonnaffé, Philippe Delannoy, Francoise Vinet, Aurélie Cazet, Isabelle Texier, Laurent Guyon, Aude Bernardin, Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Azides, Luminescence, MESH: Membrane Glycoproteins, Biomedical Engineering, Pharmaceutical Science, MESH: Cricetinae, Bioengineering, Nanotechnology, CHO Cells, 010402 general chemistry, 01 natural sciences, Cricetulus, MESH: Cricetulus, MESH: CHO Cells, Cricetinae, Quantum Dots, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Copper-free click chemistry, Pharmacology, chemistry.chemical_classification, Membrane Glycoproteins, MESH: Molecular Imaging, 010405 organic chemistry, Biomolecule, MESH: Luminescence, Organic Chemistry, Cell Membrane, MESH: Quantum Dots, MESH: Azides, Cycloaddition, N-Acetylneuraminic Acid, 0104 chemical sciences, Molecular Imaging, MESH: Copper, chemistry, Quantum dot, Alkynes, Click chemistry, Surface modification, MESH: N-Acetylneuraminic Acid, Biological imaging, MESH: Alkynes, Copper, Biotechnology, MESH: Cell Membrane
Abstract

International audience; Quantum dots (QD) are inorganic nanocrystals with outstanding optical properties, specially suited for biological imaging applications. Their attachment to biomolecules in mild aqueous conditions for the design of bioconjugates is therefore highly desirable. 1,3-dipolar [3 + 2] cycloaddition between azides and terminal alkynes ("click chemistry") could represent an attractive QD functionalization method. Unfortunately, the use of the popular Cu(I)-catalyzed version of this reaction is not applicable for achieving this goal, since the presence of copper dramatically alters the luminescence properties of QD dispersions. We demonstrate here that copper-free click chemistry, between strained cyclooctyne functionalized QD and azido-biomolecules, leads to highly luminescent conjugates. In addition, we show that QD-cyclooctyne can be used at previously unreported low concentration (250 nM) for imaging the incorporation of azido-modified sialic acid in cell membrane glycoproteins.

Published
2010

24. Effects of copper on the photosynthesis of intact chloroplasts: interaction with manganese

Author

Mário Pádua, Serge Aubert, Richard Bligny, Adalcina Casimiro, Ana M. Cavaco, Escola Superior de Tecnologia da Saude de Lisboa, Centro de Electronica, Optoelectronica e Telecomunicaçoes [Faro] (CEOT), Universidade do Algarve (UAlg), Station alpine Joseph Fourier - UMS 3370 (SAJF), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Departamento de Biologia Vegetal, Faculdade de Ciencias da Universidade de Lisboa, Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Chlorophyll, 0106 biological sciences, Chloroplasts, Photoinhibition, photosynthesis inhibition, Photosystem II, Physiology, plant, Plant Science, Photochemistry, MESH: Carbon Dioxide, 01 natural sciences, Chloroplast membrane, stress, Spinacia oleracea, MESH: Oxygen Consumption, Photosynthesis, Chlorophyll fluorescence, MESH: Photosynthesis, 0303 health sciences, MESH: Spinacia oleracea, MESH: Photosystem II Protein Complex, food and beverages, General Medicine, Chloroplast, MESH: Copper, Thylakoid, manganese, MESH: Chlorophyll, chemistry.chemical_element, MESH: Manganese, MESH: Peas, Fluorescence, 03 medical and health sciences, Oxygen Consumption, chloroplast, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Manganese, MESH: Chloroplasts, MESH: Fluorescence, Peas, Photosystem II Protein Complex, Cell Biology, Carbon Dioxide, heavy metal, Copper, chemistry, copper, metabolism, 010606 plant biology & botany
Abstract

International audience; Highly purified, intact chloroplasts were prepared from pea (Pisum sativum L.) and spinach (Spinacia oleracea L.) following an identical procedure, and were used to investigate the cupric cation inhibition on the photosynthetic activity. In both species, copper inhibition showed a similar inhibitor concentration that decreases the enzyme activity by 50% (IC(50) approximately 1.8 microM) and did not depend on the internal or external phosphate (Pi) concentration, indicating that copper did not interact with the Pi translocator. Fluorescence analysis suggested that the presence of copper did not facilitate photoinhibition, because there were no changes in maximal fluorescence (F(m)) nor in basal fluorescence (F(o)) of copper-treated samples. The electron transport through the photosystem II (PSII) was also not affected (operating efficiency of PSII-F'v/F'm similar in all conditions). Yet, under Cu(2+) stress, the proportion of open PSII reaction centers was dramatically decreased, and the first quinone acceptor (Q(A)) reoxidation was fully inhibited, as demonstrated by the constant photochemical quenching (q(P)) along experiment time. The quantum yield of PSII electron transport (Phi(PSII)) was also clearly affected by copper, and therefore reduced the photochemistry efficiency. Manganese, when added simultaneously with copper, delayed the inhibition, as measured by oxygen evolution and chlorophyll fluorescence, but neither reversed the copper effect when added to copper-inhibited plastids, nor prevented the inhibition of the Hill activity of isolated copper-treated thylakoids. Our results suggest that manganese competed with copper to penetrate the chloroplast envelope. This competition seems to be specific because other divalent cations e.g. magnesium and calcium, did not interfere with the copper action in intact chloroplasts. All results do suggest that, under these conditions, the stroma proteins, such as the Calvin-Benson cycle enzymes or others are the most probable first target for the Cu(2+) action, resulting in the total inhibition of chloroplast photosynthesis and in the consequent unbalanced rate of production and consumption of the reducing power.

Published
2010

25. Peptidylglycine α-amidating monooxygenase activity and TRH and CRF biosynthesis

Author

Françpise Boudouresque, L'Houcine Ouafik, Pierre Giraud, J. Y. Maltese, P. Salers, Charles Oliver, François Pelen, M Renard, INSERM U 297 - Laboratoire de Neuroendocrinologie Expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM), and Ouafik, L'Houcine

Subjects
Corticotropin-Releasing Hormone, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Thyrotropin-releasing hormone, MESH: Amino Acid Sequence, MESH: Multienzyme Complexes, MESH: Chelating Agents, Biochemistry, Mixed Function Oxygenases, chemistry.chemical_compound, Corticotropin-releasing hormone, Insulin, MESH: Animals, Thyrotropin-Releasing Hormone, Cells, Cultured, Chelating Agents, Biological activity, General Medicine, MESH: Mixed Function Oxygenases, MESH: Corticotropin-Releasing Hormone, MESH: Copper, Hypothalamus, Ditiocarb, Peptidylglycine alpha-amidating monooxygenase, MESH: Ditiocarb, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured, endocrine system, MESH: Rats, Molecular Sequence Data, Neuropeptide, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Insulin, Inorganic Chemistry, Islets of Langerhans, Fetus, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biosynthesis, MESH: Thyrotropin-Releasing Hormone, Multienzyme Complexes, Animals, Amino Acid Sequence, MESH: Molecular Sequence Data, MESH: Islets of Langerhans, Biochemistry (medical), MESH: Fetus, Monooxygenase, MESH: Hypothalamus, Rats, chemistry, Copper
Abstract

International audience; Carboxy-terminal amidation of biologically active peptides, an important characteristic of more than half of these substances, occurs during the maturation process of peptide precursors. It is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM), an enzyme that is copper-dependent. We show here that alterations of copper stores in cultured cells from different origins (pancreas and hypothalamus) affect the immunoreactivity of thyrotropin-releasing hormone (TRH) and corticotropin-releasing factor (CRF) (two alpha-amidated peptides). This suggests that copper can affect neuropeptide biosynthesis and may play a role in the endocrine or central nervous system function.

Published
1992

26. Isolation and characterization of a new Cu-Fe protein from Desulfovibrio aminophilus DSM12254

Author

Guy Fauque, Sofia R. Pauleta, Cristiano Mota, Alice S. Pereira, Filipe Folgosa, Maria G. Rivas, José J. G. Moura, Susana L. A. Andrade, Marta S. P. Carepo, Juan J. Calvete, Isabel Moura, Pedro Tavares, Departamento de Quimica (REQUIMTE), Universidade de Lisboa = University of Lisbon (ULISBOA)-Centro de Quimica Fina e Biotecnologia, Institut für Organische Chemie und Biochemie [Freiburg], Albert-Ludwigs-Universität Freiburg, Laboratoire de Microbiologie et Biotechnologie des Environnements Chauds, Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1, Instituto de biomedicina [Valencia] (IBV), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), and Universidade de Lisboa (ULISBOA)-Centro de Quimica Fina e Biotecnologia

Subjects
MESH: Drug Resistance, Bacterial: drug effects,physiology, Iron, Inorganic chemistry, chemistry.chemical_element, Zinc, Dithionite, Biochemistry, Inorganic Chemistry, Metal, 03 medical and health sciences, chemistry.chemical_compound, MESH: Metalloproteins: chemistry,genetics,isolation & purification,metabolism, Bacterial Proteins, MESH: Bacterial Proteins: chemistry,genetics,isolation & purification,metabolism, Drug Resistance, Bacterial, Metalloproteins, Metalloprotein, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein Structure, Quaternary, Peptide sequence, 030304 developmental biology, MESH: Protein Structure, Quaternary: physiology, Molybdenum, chemistry.chemical_classification, 0303 health sciences, MESH: Iron, biology, Molecular mass, 030306 microbiology, MESH: Desulfovibrio: chemistry,genetics,metabolism, biology.organism_classification, Desulfovibrio, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Copper, Crystallography, chemistry, visual_art, visual_art.visual_art_medium, MESH: Molybdenum: chemistry,pharmacology, Copper, DNA
Abstract

The isolation and characterization of a new metalloprotein containing Cu and Fe atoms is reported. The as-isolated Cu-Fe protein shows an UV-visible spectrum with absorption bands at 320 nm, 409 nm and 615 nm. Molecular mass of the native protein along with denaturating electrophoresis and mass spectrometry data show that this protein is a multimer consisting of 14+/-1 subunits of 15254.3+/-7.6 Da. Mössbauer spectroscopy data of the as-isolated Cu-Fe protein is consistent with the presence of [2Fe-2S](2+) centers. Data interpretation of the dithionite reduced protein suggest that the metallic cluster could be constituted by two ferromagnetically coupled [2Fe-2S](+) spin delocalized pairs. The biochemical properties of the Cu-Fe protein are similar to the recently reported molybdenum resistance associated protein from Desulfovibrio, D. alaskensis. Furthermore, a BLAST search from the DNA deduced amino acid sequence shows that the Cu-Fe protein has homology with proteins annotated as zinc resistance associated proteins from Desulfovibrio, D. alaskensis, D. vulgaris Hildenborough, D. piger ATCC 29098. These facts suggest a possible role of the Cu-Fe protein in metal tolerance.

Published
2009

27. Iron excess treatable by copper supplementation in acquired aceruloplasminemia: a new form of secondary human iron overload?

Author

Marie-Bérengère Troadec, Dorothée Videt-Gibou, Edouard Bardou-Jacquet, Serge Belliard, Joseph Rivalan, Olivier Loréal, Caroline Le Lan, Anne-Marie Jouanolle, Pierre Brissot, Service de neurologie [Rennes], Université de Rennes (UR), Régulations des équilibres fonctionnels du foie normal et pathologique, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique moléculaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Le Corre, Morgane

Subjects
medicine.medical_specialty, 030309 nutrition & dietetics, Immunology, MESH: Metal Metabolism, Inborn Errors, Iron overload disorder, chemistry.chemical_element, MESH: Dietary Supplements, Biochemistry, 03 medical and health sciences, MESH: Iron Overload, Internal medicine, medicine, CERULOPLASMIN DEFICIENCY, Aceruloplasminemia, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, MESH: Humans, MESH: Middle Aged, biology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, Hematology, medicine.disease, Copper, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH: Copper, Endocrinology, chemistry, biology.protein, Ceruloplasmin
Abstract

To the editor: Ceruloplasmin plays a major role in iron mobilization from the tissues stores through its ferroxidase activity.[1][1],[2][2] Hereditary aceruloplasminemia is an autosomal recessive iron overload disorder resulting from mutations in the ceruloplasmin gene.[3][3],[4][4] Acquired

Published
2009

28. Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men

Author

Michel Lagarde, Evelyne Véricel, Michel Guichardant, Nicolas Guillot, Catherine Calzada, Romain A. Colas, Martine Laville, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète', Groupe Lipides et Nutrition (GLN) and Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète'., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète',Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète', Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vericel, Evelyne, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, n-3 Polyunsaturated fatty acids Antioxidant Peroxidation Low-density lipoproteins, MESH: Lipoproteins, LDL, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], alpha-Tocopherol, MESH: Dietary Supplements, MESH: Lipid Peroxidation, Antioxidants, Lipid peroxidation, Cohort Studies, chemistry.chemical_compound, MESH: Vitamin E, Malondialdehyde, Vitamin E, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Fatty Acids, food and beverages, MESH: Fatty Acids, Unsaturated, Middle Aged, Eicosapentaenoic acid, 3. Good health, MESH: Fatty Acids, MESH: Copper, Lipoproteins, LDL, MESH: Docosahexaenoic Acids, Biochemistry, MESH: alpha-Tocopherol, Docosahexaenoic acid, Low-density lipoprotein, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, MESH: Oxygen, Polyunsaturated fatty acid, medicine.medical_specialty, Docosahexaenoic Acids, MESH: Malondialdehyde, 03 medical and health sciences, Internal medicine, medicine, Humans, Unsaturated fatty acid, 030304 developmental biology, Aged, MESH: Humans, MESH: Antioxidants, MESH: Male, Oxygen, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Dietary Supplements, Lipid Peroxidation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Copper, Lipoprotein
Abstract

International audience; OBJECTIVE: To determine the effect of supplementation with increasing doses of docosahexaenoic acid (DHA), as the only n-3 polyunsaturated fatty acid (PUFA), on low-density lipoprotein (LDL) redox status and oxidizability. METHODS: Twelve healthy men aged 53-65 years ingested consecutive doses of DHA (200, 400, 800 and 1600 mg/day), each dose for two weeks. RESULTS: The proportions of DHA increased dose-dependently in LDL phospholipids and cholesteryl esters, even after two weeks of supplementation with 200mg/day DHA. The daily intake of 200, 400 and 800 mg DHA resulted in increased alpha-tocopherol concentrations, decreased MDA concentrations, and a longer lag time for copper-induced LDL oxidation. Supplementation with 1600 mg/day DHA had no effect on the above parameters. In plasma, concentrations of 4-hydroxy-hexenal, specifically derived from the peroxidation of n-3 fatty acids, significantly increased after 800 and 1600 mg DHA, representing 0.01% of plasma n-3 PUFAs, while 4-hydroxy-nonenal concentrations, derived from the peroxidation of n-6 fatty acids, did not change. CONCLUSION: Our results clearly show that an intake of 200-800 mg/day DHA may have protective and antioxidant effects on LDL and could represent optimal doses for cardiovascular disease prevention in a healthy population.

Published
2009

29. X-ray structure of the metal-sensor CnrX in both the apo- and copper-bound forms

Author

Jacques Covès, Serge Gambarelli, Eric Girard, Antoine P. Maillard, Guillaume Pompidor, Richard Kahn, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Metal-sensor, Protein Conformation, [SDV]Life Sciences [q-bio], MESH: Amino Acid Sequence, Signal transduction, Crystallography, X-Ray, 01 natural sciences, Biochemistry, chemistry.chemical_compound, MESH: Apoproteins, MESH: Protein Structure, Tertiary, Protein structure, MESH: Protein Conformation, Structural Biology, Cupriavidus metallidurans CH34, MESH: Bacterial Proteins, 0303 health sciences, biology, Resolution (electron density), Cupriavidus, 3. Good health, MESH: Copper, visual_art, visual_art.visual_art_medium, Periplasmic Proteins, Dimerization, Stereochemistry, Molecular Sequence Data, Biophysics, chemistry.chemical_element, CnrX, 010402 general chemistry, Metal, 03 medical and health sciences, Bacterial Proteins, Genetics, Amino Acid Sequence, Molecular Biology, 030304 developmental biology, MESH: Cupriavidus, MESH: Molecular Sequence Data, Cupriavidus metallidurans, Ligand, Cell Biology, biology.organism_classification, MESH: Crystallography, X-Ray, Copper, 0104 chemical sciences, Protein Structure, Tertiary, Crystallography, chemistry, MESH: Dimerization, X-ray structure, Apoproteins, Derivative (chemistry), Heavy-metal, MESH: Periplasmic Proteins
Abstract

International audience; Both the X-ray structures of the apo- and the copper-bound forms of the metal-sensor domain (residues 31-148) of CnrX from Cupriavidus metallidurans CH34 were obtained at 1.74A resolution from a selenomethionine derivative. This four-helix hooked-hairpin is the first structure of a metal-sensor in an ECF-type signaling pathway. The copper ion is bound in a type 2-like center with a 3N1O coordination in the equatorial plane and shows an unprecedented remote fifth axial ligand with Met93 contributing a weak S-Cu bond. The signal onset cannot be explained by conformational changes associated with CnrX metallation.

Published
2008

30. Cu2+ SPEEDS UP MAUROTOXIN OXIDATIVE FOLDING

Author

Regaya, Imed, Andreotti, Nicolas, Di Luccio, Eric, de Waard, Michel, Sabatier, Jean-Marc, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Unité de Protéomie Fonctionnelle & Bioconservation Alimentaire, Institut Supérieur des Sciences Biologiques et Appliquées de Tunis, Canaux calciques , fonctions et pathologies, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was financially supported by the CEA, INSERM, Cellpep S.A. (Paris, France), and CNRS., Collaboration, and Canepari, Marco

Subjects
musculoskeletal diseases, MESH: Oxidation-Reduction, scorpion toxin, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Protein Folding, MESH: Protein Structure, Secondary, MESH: Amino Acid Sequence, Cu2+, MESH: Circular Dichroism, disulphide bridging, MESH: Scorpion Venoms, MESH: Mice, Inbred C57BL, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Animals, MESH: Disulfides, MESH: Mice, mass spectrometry, MESH: Neurotoxins, MESH: Iodoacetamide, MESH: Alkylation, MESH: Molecular Sequence Data, MESH: Copper, maurotoxin, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, oxidative folding
Abstract

International audience; Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide bridges that acts on various K+ channel types. It folds according to an alpha/beta scaffold, i.e., a helix connected to a two stranded beta-sheet by two disulphide bridges. In a former study, various parameters that affect the oxidation and folding of the reduced form of synthetic MTX were investigated in vitro. It was found that MTX achieves its final 3-D structure by evolving over time through a series of oxidation intermediates, from the least to the most oxidized species. MTX oxidative intermediates can be studied by iodoacetamide alkylation of free cysteine residues followed by mass spectrometry analysis. Here, we have analysed the effect of Cu2+ (0.1 to 50 mM) on the kinetics of MTX oxidative folding and found that it dramatically speeds up the formation of the four-disulphide bridged, native-like, MTX (maximal production within 30 minutes instead of > 60 hours). This catalysing effect of Cu2+ was found to be concentration-dependent, reaching a plateau at 10 mM copper ions. Cu2+ was also found to prevent the slow transition of a three disulphide-bridged MTX intermediate towards the final four disulphide-bridged product (12% of total MTX). The data are discussed in light of the potential effects of Cu2+ on MTX secondary structure formation, disulphide bridging and peptidyl prolyl cis-trans isomerization.

Published
2008

31. Cu2+ SPEEDS UP MAUROTOXIN OXIDATIVE FOLDING

Author

Regaya, Imed, Andreotti, Nicolas, Di Luccio, Eric, De Waard, Michel, Sabatier, Jean-Marc, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Unité de Protéomie Fonctionnelle & Bioconservation Alimentaire, Institut Supérieur des Sciences Biologiques et Appliquées de Tunis, Canaux calciques , fonctions et pathologies, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was financially supported by the CEA, INSERM, Cellpep S.A. (Paris, France), and CNRS., and Collaboration

Subjects
musculoskeletal diseases, MESH: Alkylation, MESH: Oxidation-Reduction, MESH: Molecular Sequence Data, scorpion toxin, MESH: Protein Folding, Cu2+, MESH: Protein Structure, Secondary, MESH: Amino Acid Sequence, MESH: Circular Dichroism, MESH: Copper, maurotoxin, disulphide bridging, MESH: Scorpion Venoms, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, MESH: Mice, Inbred C57BL, oxidative folding, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Animals, MESH: Disulfides, MESH: Mice, mass spectrometry, MESH: Neurotoxins, MESH: Iodoacetamide
Abstract

International audience; Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide bridges that acts on various K+ channel types. It folds according to an alpha/beta scaffold, i.e., a helix connected to a two stranded beta-sheet by two disulphide bridges. In a former study, various parameters that affect the oxidation and folding of the reduced form of synthetic MTX were investigated in vitro. It was found that MTX achieves its final 3-D structure by evolving over time through a series of oxidation intermediates, from the least to the most oxidized species. MTX oxidative intermediates can be studied by iodoacetamide alkylation of free cysteine residues followed by mass spectrometry analysis. Here, we have analysed the effect of Cu2+ (0.1 to 50 mM) on the kinetics of MTX oxidative folding and found that it dramatically speeds up the formation of the four-disulphide bridged, native-like, MTX (maximal production within 30 minutes instead of > 60 hours). This catalysing effect of Cu2+ was found to be concentration-dependent, reaching a plateau at 10 mM copper ions. Cu2+ was also found to prevent the slow transition of a three disulphide-bridged MTX intermediate towards the final four disulphide-bridged product (12% of total MTX). The data are discussed in light of the potential effects of Cu2+ on MTX secondary structure formation, disulphide bridging and peptidyl prolyl cis-trans isomerization.

Published
2008

32. ATP7B copper-regulated traffic and association with the tight junctions: copper excretion into the bile

Author

Hernandez, Sonia, Tsuchiya, Yo, García-Ruiz, Josefa, Lalioti, Vassiliki, Nielsen, Søren, Cassio, Doris, Sandoval, Ignacio, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), The Water and Salt Research Center, Signalisation cellulaire et calcium, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants of the Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903, GEN2003-20662-C07-06) to I.V.S., and Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903

Subjects
MESH: Humans, MESH: Cell Line, Tumor, MESH: Rats, MESH: Microscopy, Fluorescence, MESH: Rats, Wistar, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, digestive system, MESH: Male, MESH: Hepatocytes, MESH: Copper, MESH: Liver Neoplasms, Experimental, MESH: Cation Transport Proteins, MESH: Antibodies, Neoplasm, MESH: Liver Neoplasms, MESH: Adenosine Triphosphatases, MESH: Blotting, Western, MESH: Animals, MESH: Carcinoma, Hepatocellular, MESH: Bile, MESH: Liver, MESH: Electrophoresis, Polyacrylamide Gel
Abstract

International audience; BACKGROUND & AIMS: The copper transporter ATP7B plays a central role in the elimination of excess copper by the liver into the bile, yet the site of its action remains controversial. The studies reported here examine the correspondence between the site of ATP7B action and distribution and the pathways of copper disposal by the liver. METHODS: Microscopy and cell fractionation studies of polarized Can 10 cells forming long-branched bile canaliculi have been used to study the cellular distribution of ATP7B. Copper excretion into the bile was studied in perfused rat liver. RESULTS: Copper excess provokes a massive download of the ATP7B retained in the trans-Golgi network into the bile canalicular membrane. Furthermore, a stable ATP7B pool is localized to the tight junctions that seal the bile canaliculi. The profile of Cu(64) excretion into the bile by isolated rat livers perfused under one-pass conditions provides evidence of copper excretion by 2 separate mechanisms, transcytosis across the hepatocyte and paracellular transport throughout the tight junctions. CONCLUSIONS: Whereas the ATP7B retained in the trans-Golgi-network is massively translocated to the bile canalicular membrane in response to increased copper levels, a pool of ATP7B associated with the tight junctions remains stable. In situ studies indicate that copper is excreted into the bile by 2 separate pathways. The results are discussed in the frame of the normal and impeded excretion of copper into the bile.

Published
2008

33. ATP7B copper-regulated traffic and association with the tight junctions: copper excretion into the bile.: ATP7B and copper excretion by liver

Author

Hernandez, Sonia, Tsuchiya, Yo, García-Ruiz, Josefa, Lalioti, Vassiliki, Nielsen, Søren, Cassio, Doris, Sandoval, Ignacio, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), The Water and Salt Research Center, Signalisation cellulaire et calcium, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants of the Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903, GEN2003-20662-C07-06) to I.V.S., Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903, and U757, .

Subjects
MESH: Humans, MESH: Cell Line, Tumor, MESH: Rats, MESH: Microscopy, Fluorescence, MESH: Rats, Wistar, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, digestive system, MESH: Male, MESH: Hepatocytes, MESH: Copper, MESH: Liver Neoplasms, Experimental, MESH: Cation Transport Proteins, MESH: Antibodies, Neoplasm, MESH: Liver Neoplasms, MESH: Adenosine Triphosphatases, MESH: Blotting, Western, MESH: Animals, MESH: Carcinoma, Hepatocellular, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Bile, MESH: Liver, MESH: Electrophoresis, Polyacrylamide Gel
Abstract

International audience; BACKGROUND & AIMS: The copper transporter ATP7B plays a central role in the elimination of excess copper by the liver into the bile, yet the site of its action remains controversial. The studies reported here examine the correspondence between the site of ATP7B action and distribution and the pathways of copper disposal by the liver. METHODS: Microscopy and cell fractionation studies of polarized Can 10 cells forming long-branched bile canaliculi have been used to study the cellular distribution of ATP7B. Copper excretion into the bile was studied in perfused rat liver. RESULTS: Copper excess provokes a massive download of the ATP7B retained in the trans-Golgi network into the bile canalicular membrane. Furthermore, a stable ATP7B pool is localized to the tight junctions that seal the bile canaliculi. The profile of Cu(64) excretion into the bile by isolated rat livers perfused under one-pass conditions provides evidence of copper excretion by 2 separate mechanisms, transcytosis across the hepatocyte and paracellular transport throughout the tight junctions. CONCLUSIONS: Whereas the ATP7B retained in the trans-Golgi-network is massively translocated to the bile canalicular membrane in response to increased copper levels, a pool of ATP7B associated with the tight junctions remains stable. In situ studies indicate that copper is excreted into the bile by 2 separate pathways. The results are discussed in the frame of the normal and impeded excretion of copper into the bile.

Published
2008

34. Cyclic AMP-dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper-ATPase

Author

Adalberto Vieyra, Elisabeth Mintz, Rafael H.F. Valverde, Jennifer Lowe, Martine Cuillel, Isabelle Morin, Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
ATPase, MESH: Catalytic Domain, MESH: Amino Acid Sequence, Biochemistry, MESH: Saccharomyces cerevisiae Proteins, Copper Transport Proteins, Structural Biology, ATP hydrolysis, Catalytic Domain, Serine, Phosphorylation, Cation Transport Proteins, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Copper transport, MESH: Saccharomyces cerevisiae, Transport protein, MESH: Copper, Asparagine, Intracellular, Cell signalling, Saccharomyces cerevisiae Proteins, MESH: Asparagine, MESH: Mutation, Molecular Sequence Data, Biophysics, chemistry.chemical_element, Saccharomyces cerevisiae, Regulatory phosphorylation, Catalysis, 03 medical and health sciences, MESH: Cation Transport Proteins, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH: Serine, Protein kinase A, Molecular Biology, 030304 developmental biology, Cyclic AMP-Dependent Protein Kinase Catalytic Subunits, MESH: Molecular Sequence Data, MESH: Phosphorylation, MESH: Cyclic AMP-Dependent Protein Kinase Catalytic Subunits, Cell Biology, MESH: Catalysis, Copper, Yeast, chemistry, Catalytic cycle, Ccc2p, Mutation, biology.protein
Abstract

International audience; The pathogenesis of human Menkes and Wilson diseases depends on alterations in copper transport. Some reports suggest that intracellular traffic of copper might be regulated by kinase-mediated phosphorylation. However, there is no evidence showing the influence of kinase-related processes in coupled ATP hydrolysis/copper transport cycles. Here, we show that cyclic AMP-dependent protein kinase (PKA) regulates Ccc2p, the yeast Cu(I)-ATPase, with PKA-mediated phosphorylation of a conserved serine (Ser258) being crucial for catalysis. Long-range intramolecular communication between Ser258 and Asp627 (at the catalytic site) modulates the key pumping event: the conversion of the high-energy to the low-energy phosphorylated intermediate associated with copper release.

Published
2008

35. Facilitated transport of diuron and glyphosate in high copper vineyard soils

Author

Philippe C. Baveye, Francis Andreux, Sylvie Dousset, Nathalie Guichard, Astrid R. Jacobson, Jean-Baptiste Dessogne, Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Plant, Soils and Climate Department, Utah State University (USU), Université de Reims Champagne-Ardenne (URCA), SIMBIOS Centre, University of Abertay Dundee, Microbiologie du Sol et de l'Environnement (MSE), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Utah State University ( USU ), Université de Reims Champagne-Ardenne ( URCA ), Microbiologie du Sol et de l'Environnement ( MSE ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), and Abertay University (Abertay University)

Subjects
MESH: Drug Interactions, 010501 environmental sciences, 01 natural sciences, MESH : Soil Pollutants, Soil, chemistry.chemical_compound, [SDU.STU.GC]Sciences of the Universe [physics]/Earth Sciences/Geochemistry, Soil pH, Soil Pollutants, Drug Interactions, MESH : Environmental Monitoring, Leaching (agriculture), MESH : Copper, 2. Zero hunger, 04 agricultural and veterinary sciences, Soil contamination, 6. Clean water, MESH: Glycine, MESH: Copper, [ SDE.MCG ] Environmental Sciences/Global Changes, MESH : Glycine, MESH : Herbicides, Glyphosate, MESH: Diuron, Protons, Calcareous, MESH: Environmental Monitoring, Environmental Monitoring, [SDE.MCG]Environmental Sciences/Global Changes, Glycine, [ SDV.SA.SDS ] Life Sciences [q-bio]/Agricultural sciences/Soil study, chemistry.chemical_element, MESH : Diuron, [SDV.SA.SDS]Life Sciences [q-bio]/Agricultural sciences/Soil study, MESH: Soil, MESH : Soil, MESH : Adsorption, [ SDU.ENVI ] Sciences of the Universe [physics]/Continental interfaces, environment, MESH : Protons, Environmental Chemistry, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, 0105 earth and related environmental sciences, MESH: Herbicides, MESH: Soil Pollutants, Herbicides, General Chemistry, 15. Life on land, [ SDU.STU.GC ] Sciences of the Universe [physics]/Earth Sciences/Geochemistry, Copper, MESH : Drug Interactions, Soil conditioner, chemistry, Agronomy, 13. Climate action, Diuron, Soil water, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Adsorption, MESH: Protons, MESH: Adsorption
Abstract

6 pages; International audience; The fate of organic herbicides applied to agricultural fields may be affected by other soil amendments, such as copper applied as a fungicide. The effect of copper on the leaching of diuron and glyphosate through a granitic and a calcareous soil was studied in the laboratory using sieved-soil columns. Each soil was enriched with copper sulfate to obtain soil copper concentrations of 125, 250, 500, and 1000 mg kg(-1). Glyphosate leaching was influenced by soil pH and copper concentration, whereas diuron leaching was not. In the calcareous soil, glyphosate leaching decreased as copper levels increased from 17 mg kg(-1) (background) to 500 mg kg(-1). In the granitic soil, glyphosate leaching increased as copper levels increased from 34 mg kg(-1) (background) to 500 mg kg(-1). The shapes of the copper elution curves in presence of glyphosate were similar to shapes of the glyphosate curves, suggesting the formation of Cu-glyphosate complexes that leach through the soil. Soil copper concentration does not influence diuron leaching. In contrast, increasing copper concentrations reduces glyphosate leaching through calcareous soils, and conversely, increases glyphosate leaching through granitic soils. Our findings suggest that the risk of groundwater contamination by glyphosate increases in granitic soils with elevated copper concentrations.

Published
2007

36. Study of Cu chemical state inside single neurons from Parkinson's disease and control substantia nigra using the micro-XANES technique

Author

Marek Lankosz, Magdalena Szczerbowska-Boruchowska, Sylvain Bohic, Dariusz Adamek, Joanna Chwiej, Anna Krygowska-Wajs, Serduc, Raphael, Department of Applied Nuclear Physics, Faculty of Physics and Applied Computer Science-AGH University of Science and Technology [Krakow, PL] (AGH UST), Institute of Neurology, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collaboration, and Collegium Medicum, Jagiellonian University

Subjects
Parkinson's disease, MESH: Neurons, MESH: Substantia Nigra, Substantia nigra, MESH: Spectrum Analysis, Protein aggregation, 01 natural sciences, Biochemistry, Absorption, Inorganic Chemistry, 03 medical and health sciences, MESH: X-Rays, Nuclear magnetic resonance, Oxidation state, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Spectroscopy, 030304 developmental biology, Neurons, 0303 health sciences, Chemistry, Spectrum Analysis, X-Rays, 010401 analytical chemistry, MESH: Absorption, Trace element, Parkinson Disease, medicine.disease, XANES, 0104 chemical sciences, MESH: Copper, Substantia Nigra, Chemical state, Molecular Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Parkinson Disease, Copper
Abstract

International audience; Parkinson's disease (PD) is referred to as idiopathic disorder, which means that its causes have not been found yet. However, a few processes such as oxidative stress, protein aggregation and mitochondrial dysfunction are suspected to lead to the atrophy and death of substantia nigra (SN) neurons in case of this neurodegenerative disorder. Cu is a trace element whose role in the pathogenesis of PD is widely discussed. The investigation of Cu oxidation state inside single nerve cells from SN of PD and control cases may shed some new light on the role of this element in PD. The differences in Cu chemical state were investigated with the use of X-ray absorption near edge structure (XANES) spectroscopy. The least-square fitting method was applied for the analysis of XANES spectra. The comparison of the positions of white line, multiple scattering and pre-edge peak maximum at the energy scale did not reveal the existence of differences in Cu chemical state between PD and control samples. However, it was found that most of the Cu inside SN neurons occurs in tetrahedral environment and probably as Cu(II).

Published
2007

37. On-resin cyclization of peptide ligands of the Vascular Endothelial Growth Factor Receptor 1 by copper(I)-catalyzed 1,3-dipolar azide–alkyne cycloaddition

Author

Pascale Coric, Anne Regazzetti, Michel Vidal, Benoit Gautier, Victor Goncalves, Nicolas Inguimbert, Serge Bouaziz, Christiane Garbay, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre des Matériaux des Mines d'Alès (C2MA), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie Moléculaire et Cellulaire (PMC - UMR_S 648), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Chimie des Biomolécules et de l'Environnement (LCBE), Université Montpellier 1 (UM1)-Université de Perpignan Via Domitia (UPVD), Bouaziz, Serge, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Models, Molecular, Vascular Endothelial Growth Factor A, MESH: Protein Structure, Quaternary, Clinical Biochemistry, Pharmaceutical Science, MESH: Amino Acid Sequence, Crystallography, X-Ray, Ligands, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Drug Discovery, MESH: Ligands, MESH: Cyclization, Chromatography, High Pressure Liquid, chemistry.chemical_classification, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Peptides, Cycloaddition, Cyclic peptide, MESH: Copper, Alkynes, 1,3-Dipolar cycloaddition, Click chemistry, Molecular Medicine, MESH: Models, Molecular, Protein Binding, Azides, Stereochemistry, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, education, Alkyne, 010402 general chemistry, Catalysis, Growth factor receptor, MESH: Protein Binding, Amino Acid Sequence, Protein Structure, Quaternary, MESH: Chromatography, High Pressure Liquid, Molecular Biology, Vascular Endothelial Growth Factor Receptor-1, MESH: Molecular Sequence Data, MESH: Vascular Endothelial Growth Factor Receptor-1, 010405 organic chemistry, Ligand, MESH: Vascular Endothelial Growth Factor A, Organic Chemistry, MESH: Catalysis, MESH: Crystallography, X-Ray, MESH: Azides, 0104 chemical sciences, chemistry, Cyclization, Azide, Peptides, MESH: Alkynes, Copper
Abstract

International audience; Cyclic peptides were obtained, on-resin, by the copper (I) catalysed 1,3-dipolar cycloaddition of azides and alkynes. The reaction led exclusively to the formation of the expected cyclomonomeric products which acted as ligands of the Vascular Endothelial Growth Factor receptor 1.

Published
2007

38. Interplay between glutathione, Atx1 and copper. 1. Copper(I) glutathionate induced dimerization of Atx1

Author

Isabelle Morin, Elisabeth Mintz, Olivier Jacquin, Martine Cuillel, Roger Miras, Florent Guillain, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Saccharomyces cerevisiae Proteins, MESH: Protein Structure, Quaternary, Stereochemistry, Dimer, chemistry.chemical_element, MESH: Carrier Proteins, Plasma protein binding, Saccharomyces cerevisiae, 010402 general chemistry, 01 natural sciences, Biochemistry, Redox, Cofactor, Absorption, Substrate Specificity, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, MESH: Saccharomyces cerevisiae Proteins, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein Structure, Quaternary, 030304 developmental biology, MESH: Glutathione, 0303 health sciences, biology, MESH: Absorption, Glutathione, Copper, MESH: Saccharomyces cerevisiae, Yeast, 0104 chemical sciences, 3. Good health, MESH: Copper, Cytosol, Crystallography, chemistry, MESH: Dimerization, biology.protein, MESH: Substrate Specificity, Carrier Proteins, Dimerization, Protein Binding
Abstract

International audience; Copper is both an essential element as a catalytic cofactor and a toxic element because of its redox properties. Once in the cell, Cu(I) binds to glutathione (GSH) and various thiol-rich proteins that sequester and/or exchange copper with other intracellular components. Among them, the Cu(I) chaperone Atx1 is known to deliver Cu(I) to Ccc2, the Golgi Cu-ATPase, in yeast. However, the mechanism for Cu(I) incorporation into Atx1 has not yet been unraveled. We investigated here a possible role of GSH in Cu(I) binding to Atx1. Yeast Atx1 was expressed in Escherichia coli and purified to study its ability to bind Cu(I). We found that with an excess of GSH [at least two GSH/Cu(I)], Atx1 formed a Cu(I)-bridged dimer of high affinity for Cu(I), containing two Cu(I) and two GSH, whereas no dimer was observed in the absence of GSH. The stability constants (log beta) of the Cu(I) complexes measured at pH 6 were 15-16 and 49-50 for CuAtx1 and Cu (2) (I) (GS(-))(2)(Atx1)(2), respectively. Hence, these results suggest that in vivo the high GSH concentration favors Atx1 dimerization and that Cu (2) (I) (GS(-))(2)(Atx1)(2) is the major conformation of Atx1 in the cytosol.

Published
2007

39. Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase

Author

Dennis R. Winge, Fabien Pierrel, Megan Bestwick, Paul A. Cobine, University of Utah, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Glycerol, Cytoplasm, Ligands, Biochemistry, Superoxide Dismutase-1, 0302 clinical medicine, MESH: Saccharomyces cerevisiae Proteins, MESH: Ligands, MESH: Superoxide Dismutase, 0303 health sciences, MESH: Genetic Complementation Test, MESH: Oxidative Stress, biology, Ligand (biochemistry), Mitochondria, MESH: Copper, Phenotype, Mitochondrial matrix, MESH: Molecular Chaperones, Intermembrane space, Saccharomyces cerevisiae Proteins, MESH: Mitochondria, MESH: Biological Transport, SOD1, chemistry.chemical_element, MESH: Phenotype, Electron Transport Complex IV, Superoxide dismutase, 03 medical and health sciences, MESH: Electron Transport Complex IV, MESH: Glycerol, Humans, Cytochrome c oxidase, Inner membrane, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, MESH: Humans, Superoxide Dismutase, MESH: Cytoplasm, Genetic Complementation Test, MESH: Metallothionein, Biological Transport, Cell Biology, Copper, Oxidative Stress, chemistry, biology.protein, Metallothionein, 030217 neurology & neurosurgery, Molecular Chaperones
Abstract

International audience; A mitochondrial matrix copper ligand (CuL) complex, conserved in mammalian cells, is the likely source of copper for assembly of cytochrome c oxidase (CcO) and superoxide dismutase 1 (Sod1) within the intermembrane space (IMS) in yeast. Targeting the copper-binding proteins human Sod1 and Crs5 to the mitochondrial matrix results in growth impairment on non-fermentable medium caused by decreased levels of CcO. This effect is reversed by copper supplementation. Matrix-targeted Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner membrane tethered human Sod1. Copper binding by the matrix-targeted proteins attenuates levels of the CuL complex without affecting total mitochondrial copper. These data suggest that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free state.

Published
2006

40. The P174L mutation in human Sco1 severely compromises Cox17-dependent metallation but does not impair copper binding

Author

Yih-Chern Horng, Eric A. Shoubridge, Florin Sasarman, Dennis R. Winge, Fabien Pierrel, Scot C. Leary, Paul A. Cobine, University of Utah, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Human Genetics [Montréal], and McGill University = Université McGill [Montréal, Canada]

Subjects
MESH: Mutation, Mitochondrial translation, MESH: Mitochondria, Protein subunit, Mutation, Missense, MESH: Carrier Proteins, Biology, medicine.disease_cause, Biochemistry, Electron Transport Complex IV, MESH: Recombinant Proteins, 03 medical and health sciences, Copper Transport Proteins, COX17, MESH: Electron Transport Complex IV, Mutant protein, medicine, Humans, Missense mutation, Cytochrome c oxidase, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, 0303 health sciences, Mutation, MESH: Mutation, Missense, Binding Sites, MESH: Humans, 030302 biochemistry & molecular biology, Membrane Proteins, Translation (biology), Cell Biology, Fibroblasts, Molecular biology, Recombinant Proteins, Mitochondria, MESH: Copper, MESH: Binding Sites, MESH: Fibroblasts, biology.protein, MESH: Membrane Proteins, Carrier Proteins, Copper, Molecular Chaperones, Protein Binding
Abstract

International audience; Sco1 is a metallochaperone that is required for copper delivery to the Cu(A) site in the CoxII subunit of cytochrome c oxidase. The only known missense mutation in human Sco1, a P174L substitution in the copper-binding domain, is associated with a fatal neonatal hepatopathy; however, the molecular basis for dysfunction of the protein is unknown. Immortalized fibroblasts from a SCO1 patient show a severe deficiency in cytochrome c oxidase activity that was partially rescued by overexpression of P174L Sco1. The mutant protein retained the ability to bind Cu(I) and Cu(II) normally when expressed in bacteria, but Cox17-mediated copper transfer was severely compromised both in vitro and in a yeast cytoplasmic assay. The corresponding P153L substitution in yeast Sco1 was impaired in suppressing the phenotype of cells harboring the weakly functional C57Y allele of Cox17; however, it was functional in sco1delta yeast when the wild-type COX17 gene was present. Pulse-chase labeling of mitochondrial translation products in SCO1 patient fibroblasts showed no change in the rate of CoxII translation, but there was a specific and rapid turnover of CoxII protein in the chase. These data indicate that the P174L mutation attenuates a transient interaction with Cox17 that is necessary for copper transfer. They further suggest that defective Cox17-mediated copper metallation of Sco1, as well as the subsequent failure of Cu(A) site maturation, is the basis for the inefficient assembly of the cytochrome c oxidase complex in SCO1 patients.

Published
2006

41. Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus

Author

Jouvin-Marche, Evelyne, Attuil-Audenis, Valérie, Aude-Garcia, Catherine, Rachidi, Walid, Zabel, Mark, Podevin-Dimster, Valérie, Siret, Carole, Huber, Christoph, Martinic, Marianne, Riondel, Jacqueline, Villiers, Christian, Favier, Alain, Naquet, Philippe, Cesbron, Jean-Yves, Marche, Patrice, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie du stress oxydant, Université Joseph Fourier - Grenoble 1 (UJF), Neuropathology institute, University hospital of Zurich [Zurich], Transmission et pathogénèse des maladies à prions (TPMP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), 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), Institute of experimental immunology, grants from the Groupement d'Inte´reˆt Scientifique- Prion (Grants A42 and A108), the Commissariat a` l'Energie Atomique Tox- Nuc Program (Grant 13-10), and the European Union, Project Number QLK5-CT- 2002-01044. V.A.-A. is a recipient of a GIS-Prion Fellowship., and Marche, Patrice

Subjects
MESH: Cell Differentiation, MESH: Receptors, Antigen, T-Cell, alpha-beta, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Oxydative Stress, MESH: Antioxidants, MESH: Dietary Supplements, MESH: Thymus Gland, MESH: Phenotype, MESH: Gene Expression Regulation, Thymus, MESH: Copper, MESH: Prions, MESH: T-Lymphocytes, MESH: Mice, Inbred C57BL, Prion, T lymphocyte, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Antigens, CD, MESH: Mice
Abstract

E.J.-M, V.A.-A. and C.A.-G. contributed equally to this work.; International audience; Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.

Published
2006

42. Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus

Author

Jacqueline Riondel, Jean-Yves Cesbron, Marianne M. A. Martinic, Valérie Attuil-Audenis, Catherine Aude-Garcia, Alain Favier, Carole Siret, Patrice N. Marche, Evelyne Jouvin-Marche, Christian L. Villiers, Christoph Huber, Philippe Naquet, Valérie Podevin-Dimster, Walid Rachidi, Mark D. Zabel, Contrôle moléculaire de la réponse immune specifique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de biologie du stress oxydant, Université Joseph Fourier - Grenoble 1 (UJF), Neuropathology institute, University hospital of Zurich [Zurich], Transmission et pathogénèse des maladies à prions (TPMP), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institute of experimental immunology, grants from the Groupement d'Inte´reˆt Scientifique- Prion (Grants A42 and A108), the Commissariat a` l'Energie Atomique Tox- Nuc Program (Grant 13-10), and the European Union, Project Number QLK5-CT- 2002-01044. V.A.-A. is a recipient of a GIS-Prion Fellowship., Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cellular differentiation, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH: Dietary Supplements, Antioxidants, Mice, 0302 clinical medicine, T lymphocyte, Immunology and Allergy, MESH: Animals, Receptor, MESH: Antigens, CD, Regulation of gene expression, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, Cell Differentiation, MESH: Gene Expression Regulation, Thymus, MESH: Copper, medicine.anatomical_structure, Phenotype, Prion, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cell Differentiation, MESH: Mice, Transgenic, Prions, Transgene, T cell, Oxydative Stress, Immunology, Context (language use), Mice, Transgenic, Thymus Gland, Biology, MESH: Phenotype, 03 medical and health sciences, MESH: Prions, Antigen, MESH: Mice, Inbred C57BL, Antigens, CD, medicine, Animals, MESH: Mice, 030304 developmental biology, MESH: Antioxidants, MESH: Thymus Gland, Molecular biology, Mice, Inbred C57BL, MESH: T-Lymphocytes, Gene Expression Regulation, Dietary Supplements, 030217 neurology & neurosurgery, Copper
Abstract

E.J.-M, V.A.-A. and C.A.-G. contributed equally to this work.; International audience; Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.

Published
2006

43. HMA1, a new Cu-ATPase of the chloroplast envelope, is essential for growth under adverse light conditions

Author

Daphné Seigneurin-Berny, Pierre Richaud, Giovanni Finazzi, Norbert Rolland, Antoine Gravot, Alexandra Kraut, Christophe Mazard, Pascaline Auroy, Jacques Joyard, Didier Grunwald, Fabrice Rappaport, Alain Vavasseur, Roux-Buisson, Nathalie, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Echanges Membranaires et Signalisation (LEMS), Université de la Méditerranée - Aix-Marseille 2-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Physiologie membranaire et moléculaire du chloroplaste (PMMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), ANTE-INSERM U836, équipe 4, Muscles et pathologies, Laboratoire Canaux Ioniques, Fonctions et Pathologies, EMI 9931 CEA/INSERM/Universite' Joseph Fourier-DRDC/ CEA-Grenoble-EMI 9931 CEA/INSERM/Universite' Joseph Fourier-DRDC/ CEA-Grenoble, This work was supported by CNRS and CEA (Toxicologie Nucléaire Environnementale) research programs., Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)

Subjects
0106 biological sciences, enveloppe chloroplastique, Chloroplasts, Light, ATPase, Mutant, Arabidopsis, MESH: Amino Acid Sequence, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 01 natural sciences, Biochemistry, Chloroplast membrane, protéine transmembranaire, Yeasts, Homeostasis, MESH: Arabidopsis, Cloning, Molecular, Plastocyanin, Cation Transport Proteins, MESH: Superoxide Dismutase, Plant Proteins, Adenosine Triphosphatases, 0303 health sciences, chloroplaste, biology, MESH: Plant Proteins, ion métallique, MESH: Yeasts, zinc, stress lumineux, food and beverages, Chloroplast, MESH: Copper, cuivre, Chloroplast DNA, plante expérimentale, MESH: Homeostasis, Copper-transporting ATPases, MESH: Mutation, Nuclear Envelope, Molecular Sequence Data, MESH: Arabidopsis Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, TRANSPORT INTRACELLULLAIRE, 03 medical and health sciences, MESH: Nuclear Envelope, MESH: Cation Transport Proteins, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Adenosine Triphosphatases, MESH: Cloning, Molecular, Amino Acid Sequence, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, homéostasie, 030304 developmental biology, Ion Transport, MESH: Molecular Sequence Data, MESH: Chloroplasts, Arabidopsis Proteins, Superoxide Dismutase, arabidopsis thaliana, Cell Biology, biology.organism_classification, MESH: Light, MESH: Ion Transport, Copper-Transporting ATPases, Mutation, biology.protein, Copper, 010606 plant biology & botany
Abstract

International audience; Although ions play important roles in the cell and chloroplast metabolism, little is known about ion transport across the chloroplast envelope. Using a proteomic approach specifically targeted to the Arabidopsis chloroplast envelope, we have identified HMA1, which belongs to the metal-transporting P1B-type ATPases family. HMA1 is mainly expressed in green tissues, and we validated its chloroplast envelope localization. Yeast expression experiments demonstrated that HMA1 is involved in copper homeostasis and that deletion of its N-terminal His-domain partially affects the metal transport. Characterization of hma1 Arabidopsis mutants revealed a lower chloroplast copper content and a diminution of the total chloroplast superoxide dismutase activity. No effect was observed on the plastocyanin content in these lines. The hma1 insertional mutants grew like WT plants in standard condition but presented a photosensitivity phenotype under high light. Finally, direct biochemical ATPase assays performed on purified chloroplast envelope membranes showed that the ATPase activity of HMA1 is specifically stimulated by copper. Our results demonstrate that HMA1 offers an additional way to the previously characterized chloroplast envelope Cu-ATPase PAA1 to import copper in the chloroplast.

Published
2006

44. New model potentials for sulfur-copper(I) and sulfur-mercury(II) interactions in proteins: From ab initio to molecular dynamics

Author

Serge Crouzy, Jean-Pierre Dognon, Jean-Francois Fuchs, Hristo Nedev, Michel Ferrand, Valérie Brenner, David Poger, Laboratoire de biophysique moléculaire et cellulaire (LBMC), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Francis PERRIN (LFP - URA 2453), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Claude Fréjacques (LCF - URA 331), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
MESH: Databases, Protein, fit from ab initio potential, MESH: Ions, metalloproteins, Static Electricity, Ab initio, chemistry.chemical_element, 010402 general chemistry, Models, Biological, 01 natural sciences, Force field (chemistry), Metal, 03 medical and health sciences, Molecular dynamics, MESH: Computer Simulation, Computational chemistry, MESH: Water, Computer Simulation, MESH: Proteins, MESH: Mercury, Databases, Protein, MESH: Static Electricity, 030304 developmental biology, Ions, 0303 health sciences, Chemistry, Ligand, Anharmonicity, MESH: Models, Biological, Proteins, Water, Mercury, General Chemistry, Copper, 0104 chemical sciences, MESH: Copper, MESH: Sulfur, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Bond length, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Computational Mathematics, molecular dynamics simulation, visual_art, visual_art.visual_art_medium, Cu(I), Hg(II), CHARMM force field, Sulfur
Abstract

We have developed new force field and parameters for copper(I) and mercury(II) to be used in molecular dynamics simulations of metalloproteins. Parameters have been derived from fitting of ab initio interaction potentials calculated at the MP2 level of theory, and results compared to experimental data when available. Nonbonded parameters for the metals have been calculated from ab initio interaction potentials with TIP3P water. Due to high charge transfer between Cu(I) or Hg(II) and their ligands, the model is restricted to a linear coordination of the metal bonded to two sulfur atoms. The experimentally observed asymmetric distribution of metal ligand bond lengths (r) is accounted for by the addition of an anharmonic (r3) term in the potential. Finally, the new parameters and potential, introduced into the CHARMM force field, are tested in short molecular dynamics simulations of two metal thiolates fragments in water. (Brooks BR et al. J Comput Chem 1983, 4, 1987.[1]) © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 837-856, 2006

Published
2006

45. New synthesis of cis 5-tert-butyl-L-proline via cuprate. Evaluation as a cis proline mimetic in a biological active octapeptide

Author

Hubert Vaudry, Hassan Oulyadi, Xavier Pannecoucke, Guillaume Dutheuil, Carine Aubry, Jean-Charles Quirion, Jérôme Leprince, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Proline, Stereochemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Structural Biology, Drug Discovery, MESH: Nuclear Magnetic Resonance, Biomolecular, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Peptide bond, Cuprate, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Polyproline helix, Pharmacology, Tert butyl, MESH: Proline, 010405 organic chemistry, Organic Chemistry, Molecular Mimicry, General Medicine, 0104 chemical sciences, MESH: Copper, chemistry, MESH: Oligopeptides, Aminal, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, MESH: Molecular Mimicry, Oligopeptides, Copper
Abstract

International audience; cis 5-tert-butyl-L-proline (Cbp) was prepared rapidly and efficiently by the addition of low-valent tert-butyl cuprate to an aminal derived from proline. [Cbp(2), D-Leu(5)]-OP was then synthesized, showing a predominant cis peptide bond conformation, as confirmed by NMR.

Published
2005

46. Triple helix formation with Drosophila satellite repeats. Unexpected stabilization by copper ions

Author

Jean-Louis Mergny, Jérôme Lacoste, Thierry Gautier, Virginie Horn, Masashi Takasugi, Laurent Lacroix, Laboratoire d'études de la différenciation et de l'adhérence cellulaires (LEDAC), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Acides nucléiques : dynamique, ciblage, et fonctions biologiques - Régulation et dynamique des génomes (ANDCFB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie moléculaire et cellulaire de la différenciation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Gautier, Thierry

Subjects
MESH: Hydrogen-Ion Concentration, Oligonucleotides, Electrophoretic Mobility Shift Assay, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biochemistry, Genome, chemistry.chemical_compound, MESH: Oligonucleotides, Heterochromatin, MESH: Magnesium, Magnesium, MESH: Animals, Base Pairing, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Intermolecular force, MESH: DNA, Hydrogen-Ion Concentration, MESH: DNA, Satellite, MESH: Copper, Drosophila melanogaster, MESH: Nucleic Acid Conformation, MESH: Heterochromatin, Triple helix, Pyrimidine, Cations, Divalent, Ultraviolet Rays, MESH: Base Pairing, chemistry.chemical_element, DNA, Satellite, MESH: Drosophila melanogaster, 03 medical and health sciences, MESH: Cations, Divalent, Animals, Electrophoretic mobility shift assay, 030304 developmental biology, Repetitive Sequences, Nucleic Acid, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Repetitive Sequences, Nucleic Acid, DNA, biology.organism_classification, Copper, Crystallography, chemistry, MESH: Electrophoretic Mobility Shift Assay, Nucleic Acid Conformation, Pyrimidine Nucleotides, MESH: Ultraviolet Rays, MESH: Pyrimidine Nucleotides
Abstract

International audience; The Drosophila melanogaster (AAGAGAG)(n) satellite repeat represents up to 1.5% of the entire fly genome and may adopt non-B DNA structures such as pyrimidine triple helices. UV melting and electrophoretic mobility shift assay experiments were used to monitor the stability of intermolecular triple helices as a function of size, pH, and backbone or base modification. Three to four repeats of the heptanucleotide motif were sufficient to allow the formation of a stable complex, especially when modified TFOs were used. Unexpectedly, low concentrations (40-100 microM) of Cu(2+) were found to favor strongly pyrimidine triplex formation under near-physiological conditions. In contrast, a much higher magnesium concentration was required to stabilize these triplexes significantly, suggesting that copper may be an essential stabilizing factor for pyrimidine triplexes.

Published
2004

47. Opposite effect of methionine-supplemented diet, a model of hyperhomocysteinemia, on plasma and liver antioxidant status in normotensive and spontaneously hypertensive rats

Author

Alain Jacqueson, Lysiane Richert, Carol Courderot-Masuyer, Alain Berthelot, Sophie Robin, Laurence Nicod, Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), and Université de Franche-Comté (UFC)

Subjects
Male, Homocysteine, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, MESH: Rats, Inbred SHR, MESH: Dietary Supplements, Transsulfuration pathway, 030204 cardiovascular system & hematology, medicine.disease_cause, Biochemistry, Rats, Inbred WKY, Antioxidants, MESH: Hypertension, chemistry.chemical_compound, 0302 clinical medicine, Methionine, Rats, Inbred SHR, Blood plasma, MESH: Thiobarbituric Acid Reactive Substances, MESH: Animals, MESH: Superoxide Dismutase, MESH: Biological Availability, MESH: Glutathione, 0303 health sciences, MESH: Iron, Nutrition and Dietetics, MESH: Oxidative Stress, MESH: Nitrites, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Catalase, Glutathione, MESH: Copper, Liver, MESH: Hyperhomocysteinemia, MESH: Nitrates, Hypertension, MESH: Rats, Inbred WKY, Hyperhomocysteinemia, medicine.medical_specialty, MESH: Rats, Iron, Biological Availability, Nitric Oxide, Thiobarbituric Acid Reactive Substances, 03 medical and health sciences, MESH: Diet, Internal medicine, MESH: Catalase, medicine, Animals, Cysteine, MESH: Homocysteine, Molecular Biology, Nitrites, 030304 developmental biology, Nitrates, Superoxide Dismutase, MESH: Antioxidants, MESH: Cysteine, medicine.disease, MESH: Male, Diet, Rats, Oxidative Stress, Blood pressure, Endocrinology, chemistry, Decreased blood pressure, MESH: Methionine, MESH: Nitric Oxide, Dietary Supplements, Oxidative stress, Copper, MESH: Liver
Abstract

International audience; Hyperhomocysteinemia is often associated with an increase in blood pressure. However our previous study has shown that methionine supplementation induced an increase in blood pressure in Wistar-Kyoto (WKY) rats and a decrease in blood pressure in spontaneously hypertensive rats (SHR) with significant differences in plasma homocysteine (Hcy) metabolites levels. Previously liver antioxidant status has been shown to be decreased in SHR compared to WKY rats. It has been suggested that oxidative stress may predispose to a decrease in NO bioavailability and induce the flux of Hcy through the liver transsulfuration pathway. Thus the aim of this study was 1) to investigate the effect of methionine supplementation on NO-derived metabolites in plasma and urine 2) to investigate whether abnormalities in Hcy metabolism may be responsible for the discrepancies observed between WKY rats and SHR concerning blood pressure and 3) to investigate whether a methionine-enriched diet, differently modified plasma and liver antioxidant status in WKY rats an SHR. We conclude that the increase in blood pressure in WKY rats is related to high plasma cysteine levels and is not due to a decrease in NO bioavailability and that the decrease in blood pressure in SHR is associated with high plasma GSH levels after methionine supplementation. So GSH synthesis appears to be stimulated by liver oxidative stress and GSH is redistributed into blood in SHR. So the great GSH synthesis can be rationalized as an autocorrective response that leads to a decreased blood pressure in SHR.

Published
2004

48. Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats

Author

Lysiane Richert, Carol Courderot-Masuyer, Laurence Nicod, Alain Berthelot, Sophie Robin, Fatiha Elhaïmeur, Sylvie Bobillier-Chaumont, Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), and Université de Franche-Comté (UFC)

Subjects
Male, Antioxidant, MESH: Swimming, Physiology, medicine.medical_treatment, MESH: Desoxycorticosterone, Hemodynamics, Blood Pressure, MESH: Physical Conditioning, Animal, MESH: Rats, Sprague-Dawley, 030204 cardiovascular system & hematology, Essential hypertension, medicine.disease_cause, Antioxidants, MESH: Hypertension, Pathogenesis, Rats, Sprague-Dawley, 0302 clinical medicine, Heart Rate, MESH: Animals, MESH: Heart Rate, Desoxycorticosterone, MESH: Glutathione, 0303 health sciences, MESH: Iron, MESH: Oxidative Stress, General Medicine, MESH: Blood Pressure, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Glutathione, Pathophysiology, MESH: Copper, Liver, Hypertension, Oxidoreductases, medicine.medical_specialty, MESH: Rats, Iron, 03 medical and health sciences, Physiology (medical), Internal medicine, Physical Conditioning, Animal, medicine, Conn Syndrome, Animals, MESH: Oxidoreductases, Swimming, 030304 developmental biology, Pharmacology, business.industry, MESH: Antioxidants, medicine.disease, MESH: Male, Rats, Oxidative Stress, Blood pressure, Endocrinology, business, Oxidative stress, Copper, MESH: Liver
Abstract

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control Sprague–Dawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension.Key words: exercise, DOCA-salt induced hypertensive rats, oxidative stress, liver.

Published
2003

49. A field method using microcosms to evaluate transfer of Cd, Cu, Ni, Pb and Zn from sewage sludge amended forest soils to Helix aspersa snails

Author

A. Gomot-de Vaufleury, Pierre-Marie Badot, Jean-Michel Carnus, M Ben Brahim, Renaud Scheifler, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre de Sfax, Institut National de la Recherche Agronomique ( INRA ), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Recherche Agronomique (INRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
MESH : Biological Availability, Health, Toxicology and Mutagenesis, MESH: Forestry, [ SDV.TOX.ECO ] Life Sciences [q-bio]/Toxicology/Ecotoxicology, 010501 environmental sciences, Toxicology, 01 natural sciences, MESH: Zinc, MESH : Soil Pollutants, Food chain, Nickel, MESH: Helix (Snails), Biomonitoring, MESH: Nickel, Soil Pollutants, MESH: Animals, MESH : Environmental Monitoring, MESH : Copper, MESH : Cadmium, MESH: Biological Availability, Sewage, biology, Chemistry, Helix (gastropod), Forestry, 04 agricultural and veterinary sciences, General Medicine, Pollution, 6. Clean water, MESH: Copper, Zinc, Metals, Environmental chemistry, MESH : Helix (Snails), [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, MESH : Lead, Microcosm, MESH: Environmental Monitoring, MESH: Lead, Cadmium, Environmental Monitoring, MESH: Cadmium, Biological Availability, Animals, MESH: Sewage, 0105 earth and related environmental sciences, Invertebrate, MESH: Soil Pollutants, MESH: Metals, Helix, Snails, MESH : Metals, MESH : Zinc, biology.organism_classification, Bioavailability, Lead, MESH : Sewage, Soil water, 040103 agronomy & agriculture, MESH : Forestry, 0401 agriculture, forestry, and fisheries, MESH : Animals, MESH : Nickel, Copper, Sludge
Abstract

International audience; Juvenile Helix aspersa snails exposed in field microcosms were used to assess the transfer of Cd, Cu, Ni, Pb and Zn from forest soils amended with liquid and composted sewage sludge. Zn concentrations and contents were significantly higher in snails exposed to liquid and composted sludge after 5 and 7 weeks of exposure, when compared with control. Trends were less clear for the other metals. Present results show that Zn, among the cocktail of metallic trace elements (MTE) coming from sewage sludge disposal, represents the principal concern for food chain transfer and secondary poisoning risks. The microcosm design used in this experiment was well suited for relatively long-term (about 2 months) active biomonitoring with H. aspersa snails. The snails quickly indicated the variations of MTE concentrations in their immediate environment. Therefore, the present study provides a simple but efficient field tool to evaluate MTE bioavailability and transfer.

Published
2002

50. Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague-Dawley rats and this is associated with increased liver oxidative stress

Author

Fatiha, Elhaïmeur, Carol, Courderot-Masuyer, Laurence, Nicod, Catherine, Guyon, Lysiane, Richert, Alain, Berthelot, Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), and Université de Franche-Comté (UFC)

Subjects
Male, MESH: Rats, Iron, MESH: Desoxycorticosterone, Blood Pressure, MESH: Dietary Supplements, Ascorbic Acid, MESH: Rats, Sprague-Dawley, Antioxidants, MESH: Hypertension, Rats, Sprague-Dawley, MESH: Catalase, Animals, MESH: Ascorbic Acid, MESH: Animals, Desoxycorticosterone, Glutathione Peroxidase, MESH: Iron, MESH: Oxidative Stress, MESH: Antioxidants, Free Radical Scavengers, MESH: Blood Pressure, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Catalase, MESH: Male, Rats, MESH: Copper, Oxidative Stress, Liver, Dietary Supplements, Hypertension, MESH: Glutathione Peroxidase, MESH: Free Radical Scavengers, Copper, MESH: Liver
Abstract

International audience; The effects of a vitamin C supplemented diet on blood pressure, body and liver weights, liver antioxidant status, iron and copper levels were investigated in DOCA-salt treated and untreated Sprague-Dawley (SD) male rats after 8 weeks of treatment. Vitamin C supplementation had no effect on blood pressure in SD rats but induced a significant decrease in blood pressure in DOCA-salt treated rats, the decrease being more efficient at 50 mg/kg of vitamin C than at 500 mg/kg. Hepatic lipid peroxidation and iron levels were significantly increased in DOCA-salt hypertensive rats whereas total hepatic antioxidant capacity (HAC), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were decreased. Vitamin C supplementation did not affect the overall antioxidant defences of control SD rat livers. In contrast, vitamin C supplementation accentuated the DOCA-salt induced accumulation of liver iron and lipid peroxidation. This occurred without any notable aggravation in the antioxidant deficiency of vitamin C supplemented DOCA-salt treated rat livers. Our data suggest that DOCA-salt treatment induces an accumulation of iron in rat livers which is responsible for the prooxidant effect of vitamin C. The normalization of blood pressure in DOCA-salt treated rats by vitamin C supplementation appears thus independent from liver antioxidant status.

Published
2002

Catalog

Books, media, physical & digital resources
See catalog results