Éditeur(s) : Université de la Polynésie Française
Résumé : The ontogeny of osmoregulation was studied in the blue shrimp Litopenaeus stylirostris in New Caledonia. The implication of branchial organs in ionic regulation was first demonstrated in juveniles by immunolocalization of three ion transporting proteins ( namely NKA, co-transporter NKCC1 and CFTR ) and ionocyte detection was done by means of electron microscopy. The role of the main ion transporting enzyme, NKA, was subsequently investigated during post-embryonic development using an integrative approach associating physiological, histological, immunological and biomolecular studies. Results obtained allowed us to propose a model of the osmoregulatory pattern in L. stylirostris based on weak regulation in the early stages, then progressively this species acquires the adult pattern of hyper-hypo-regulation after metamorphosis with the concurrent development of epipodites and gills. Strong NKA immunofluorescence and abundance of NKA transcripts in these two tissues compared to others organs suggest their functional implication in osmoregulatory processes. The results of this study allow us to increase our knowledge of the penaeid shrimp osmoregulation and to propose zootechnical measures to improve the animal physiological comfort. These propositions have been already tested during larval rearing trials, leading a two-fold-growth in 19 days-old postlarvae.
L’étude de l’ontogenèse de l’osmorégulation a été entreprise chez la crevette bleue Litopenaeus stylirostris en Nouvelle-Calédonie. L’implication des tissus de la cavité branchiale dans la régulation ionique a été déterminée au préalable chez des juvéniles par immunolocalisation de trois transporteurs protéiques d’ions, ( la NKA, le co-transporteur NKCC1 et le CFTR ) et par la détection de ionocytes en microscopie électronique. Le rôle de la NKA a été particulièrement étudié et son implication a été examinée au cours du développement post-embryonnaire par une approche intégrative associant des études physiologiques, histologiques, immunologiques et moléculaires. Cette démarche nous a permis de proposer un modèle d’osmorégulation chez L. stylirostris: de faible régulatrice dans les premiers jours de sa vie, cette espèce évolue vers l’hyper-hypo-régulation après la métamorphose avec le développement progressif des épipodites et des branchies. L’immunofluorescence prononcée de la NKA ainsi que l’abondance des transcrits du gène codant la NKA dans les tissus de ces deux organes suggèrent leur implication fonctionnelle dans l’ionorégulation. Les résultats de ce travail nous ont permis d’accroître nos connaissances sur l’osmorégulation chez les pénéidés et de proposer des améliorations zootechniques visant à augmenter leur confort physiologique. Ces préconisations ont fait l’objet de premiers essais en conditions d’élevage et se sont traduites par un doublement de la croissance des post-larves de 19 jours.

Droits : 2011 The author, Univ. Polynésie Française
http://archimer.ifremer.fr/doc/00052/16314/13816.pdf
http://archimer.ifremer.fr/doc/00052/16314/

Éditeur(s) : HAL CCSD
Résumé : International audience
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falcip-arum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P. falciparum including chloroquine-resistant isolates. Herein we have studied the antimalarial activities of dyes with different scaffold and we report that the triar-ylmethane dye (TRAM) Brilliant green inhibits the growth of asexual stages (IC 50 2 mM) and has exflagellation-blocking activity (IC 50 800 nM) against P. falciparum reference strains (3D7, 7G8) and chloroquine-resistant clinical isolate (Q206). In a second step we have investigated the antiplasmodial activities of two polysulfonated triarylmethane food dyes. Green S (E142) is weakly active against P. falciparum asexual stage (IC 50 x 17 mM) whereas Patent Blue V (E131) is inactive in both antimalarial assays. By applying liquid chromatography techniques for the culture supernatant analysis after cell washings and lysis, we report the detection of Brilliant green in erythrocytes, the selective uptake of Green S (E142) by infected erythrocytes, whereas Patent Blue V (E131) could not be detected within non-infected and 3D7-infected erythrocytes. Overall, our results suggest that two polysulfonated food dyes might display different affinity with transporters or channels on infected RBC membrane.
International journal for parasitology. Drugs and drug resistance

Droits : http://creativecommons.org/licenses/by-nc-sa/
pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/file/Leba%20LJ-article%20colorant-version%20publiee.pdf
DOI : 10.1016/j.ijpddr.2017.07.002

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0887-2333

hal-00866007
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866007
DOI : 10.1016/j.tiv.2013.07.003
PUBMED : 23850984

Éditeur(s) : Université de Bretagne Occidentale
Résumé : Study of mineral suspended particulate matter (SPM) is essential to understand ecosystem dynamics. SPM influences light penetration which is closely related to primary production and carries pollutants and nutrients within the water masses. This work aims to study near-surface mineral SPM dynamics in the English Channel using two complementary methods: remote-sensing by satellites and numerical modelling. Firstly, MODIS and MERIS satellite images processed by the IFREMER semi-analytical algorithm and describing non-algal SPM, are analysed to build three statistical models which are able to estimate near-surface SPM using simple variables, e.g., tidal coefficient, significant wave height and mean chlorophyll-a concentration. Secondly, the three-dimensional hydrosedimentary model ROMS (Regional Ocean Modeling System) is applied in the English Channel. It considers tidal forcing along open boundaries, wind stress at the sea-surface, wave-current interactions in the bottom boundary layer and realistic heterogeneous bottom sediments. Results of the more sophisticated statistical model is also used to impose SPM concentrations at open boundaries. Sensitivity tests on SPM boundary conditions show the importance of prescribing realistic sediment concentrations to improve the model predictions. Biological influences on mineral SPM are also tested using settling velocity and critical shear stress for erosion which vary with seasons. Both statistical and numerical models highlight and locate respective influences of tide, waves and biology on mineral SPM. Numerical predictions indicate that near-surface SPM is mainly composed of silts (>70%). Near-surface suspended silts come largely from seabed resuspension alongshore in the Eastern Channel and from the open boundaries of our limited-area coastal model at the West of Cotentin Peninsula and offshore. Near-surface SPM variations are investigated at semi-diurnal, neap-spring tidal cycle time scales and during a wave event. Finally, dynamics of sediments in the turbidity maximum zone around the Isle of Wight is examined depending on hydrodynamical conditions in order to distinguish the role played by advection and local erosion/settling processes in this area. Keywords: Suspended particulate matter, satellite, remote-sensing, modelling, English Channel, sediments, turbidity, tide, wave
L'étude des matières en suspension (MES) minérales est essentielle pour comprendre le fonctionnement des écosystèmes en Manche : les MES influencent la pénétration de la lumière dans la colonne d'eau, paramètre clé pour la production biologique, et sont susceptibles de transporter des polluants et nutriments. Lors de ce travail, la dynamique des MES minérales de surface en Manche est étudiée à l'aide de deux méthodes complémentaires : l'observation par satellite et la modélisation numérique tridimensionnelle. Dans un premier temps, les images satellite MODIS et MERIS, traitées par l'algorithme semi-analytique développé par l'IFREMER et représentant les MES non-algales de surface, sont analysées afin d'élaborer trois modèles statistiques permettant d'estimer la MES de surface en fonction de variables basiques telles que le coefficient de marée, la hauteur significative des vagues et la concentration moyenne en chlorophylle-a. Dans un deuxième temps, le modèle hydrosédimentaire multiclasse tridimensionnel ROMS (Regional Ocean Modeling System) est implémenté en Manche. Il prend en considération le forçage par la marée aux frontières ouvertes, la contrainte exercée par le vent à la surface de la mer, l'interaction houle-courant en couche limite de fond et l’hétérogénéité spatiale réaliste du lit sédimentaire. Les résultats du modèle statistique le plus sophistiqué sont également utilisés pour forcer la concentration en MES aux frontières ouvertes du domaine de calcul. Des tests de sensibilité sur les conditions limites montrent l'importance de considérer de manière réaliste les sédiments entrant en Manche par les frontières ouvertes lors de la modélisation numérique. L'influence de la biologie sur les MES minérales est testée en utilisant une formulation de la vitesse de chute et de la contrainte critique d'érosion variant saisonnièrement. Grâce à ces deux outils associés, les influences respectives de la marée, de la houle et de la biologie sur les MES minérales sont mises en avant et localisées en Manche. Le modèle numérique prédit que les MES de surface sont composées principalement de silts (>70%). Les silts en suspension en surface proviennent majoritairement du lit sédimentaire près des côtes en Manche orientale et des frontières ouvertes du domaine de calcul à l'ouest de la presqu'île du Cotentin et au large en Manche centrale et orientale. Les variations des MES de surface sont ensuite étudiées aux échelles des cycles de marée semi-diurnes, vive-eau/morte-eau et autour d'un épisode de houles. Enfin, l'évolution de la concentration de sédiments dans la zone de forte turbidité autour de l'île de Wight peut être analysée suivant les conditions hydrodynamiques afin d'évaluer les rôles respectifs des processus locaux d'érosion/dépot et d'advection dans la génération de ces turbidités remarquables. Mots-clés : Matière en suspension, télédétection, satellite, modélisation, Manche, sédiments, turbidité, marée, houle

Droits : 2013 UBO
http://archimer.ifremer.fr/doc/00157/26783/24884.pdf
http://archimer.ifremer.fr/doc/00157/26783/

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Zidi-Yahiaoui N, Callebaut I, Genetet S, Le Van Kim C, Cartron JP, Colin Y, Ripoche P, Mouro-Chanteloup I. Functional analysis of human RhCG: comparison with E. coli ammonium transporter reveals similarities in the pore and differences in the vestibule. Am J Physiol Cell Physiol 297: C537–C547, 2009. First published June 24, 2009; doi:10.1152/ajpcell.00137.2009.—Rh glycoproteins are members of the ammonium transporter (Amt)/methylamine permease (Mep)/Rh family facilitating movement of NH3 across plasma membranes. Homology models constructed on the basis of the experimental structures of Escherichia coli AmtB and Nitrosomonas europaea Rh50 indicated a channel structure for human RhA (RhAG), RhB (RhBG), and RhC (RhCG) glycoproteins in which external and internal vestibules are linked by a pore containing two strictly conserved histidines. The pore entry is constricted by two highly conserved phenylalanines, “twin-Phe.” In this study, RhCG function was investigated by stopped-flow spectrofluorometry measuring kinetic pH variations in HEK293E cells in the presence of an ammonium gradient. The apparent unitary NH3 permeability of RhCG was determined and was found to be close to that of AmtB. With a site-directed mutagenesis approach, critical residues involved in Rh NH3 channel activity were highlighted. In the external vestibule, the importance of both the charge and the conformation of the conserved aspartic acid was shown. In contrast to AmtB, individual mutations of each phenylalanine of the twin-Phe impaired the function while the removal of both resulted in recovery of the transport activity. The impact of the mutations suggests that, although having a common function and a similar channel structure, bacterial AmtB and human Rh vary in several aspects of the NH3 transport mechanisms.
ISSN: 0363-6143

hal-00417492
https://hal.archives-ouvertes.fr/hal-00417492
DOI : 10.1152/ajpcell.00137.2009.

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The heterodimeric L-type amino acid transporter (LAT) 1/ CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The present study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC50 values (around 0.2 μg/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98h in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development.
ISSN: 0041-008X

hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/file/Aryl%20hydrocarbon%20receptor-dependent%20up-regulation_accepted.pdf
DOI : 10.1016/j.taap.2015.11.014

Éditeur(s) : HAL CCSD Elsevier
Résumé : Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/ Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.
ISSN: 1246-7820

hal-00068842
https://hal.archives-ouvertes.fr/hal-00068842

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hepatitis B virus (HBV) infection is a major public health problem. Recently, the human liver bile acid transporter Na+/taurocholate cotransporting polypeptide (NTCP) has been identified as an HBV specific receptor. NTCP expression is known to be strongly regulated by IL-6. This study was aimed at characterizing the effect of IL-6 on HBV entry. HBV entry was inhibited by up to 90% when cells were pretreated with IL-6 as shown by a strong inhibition of long term HBsAg secretion. This effect was confirmed by showing a severe reduction of intracellular HBV cccDNA. In parallel, we observed a 98% decrease in NTCP mRNA steady state level and an 80% reduction in NTCP-mediated taurocholate uptake. IL-6-mediated inhibition of NTCP-mediated taurocholate uptake and viral entry exhibited similar dose-dependence and kinetics while restoration of NTCP expression suppressed the inhibitory effect of IL-6. NTCP-mediated HBV entry is therefore markedly inhibited by IL-6.
ISSN: 0042-6822

hal-01134184
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134184
DOI : 10.1016/j.virol.2015.02.026
PUBMED : 25765005

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.
ISSN: 1246-7820

hal-00112914
https://hal.archives-ouvertes.fr/hal-00112914
DOI : 10.1016/j.tracli.2006.02.001

Éditeur(s) : HAL CCSD
Résumé : International audience
Several forthcoming wireless telecommunication systems will use electromagnetic frequencies at millimeter waves (MMWs), and technologies developed around the 60-GHz band will soon know a widespread distribution. Free nerve endings within the skin have been suggested to be the targets of MMW therapy which has been used in the former Soviet Union. So far, no studies have assessed the impact of MMW exposure on neuronal metabolism. Here, we investigated the effects of a 24-h MMW exposure at 60.4 GHz, with an incident power density (IPD) of 5 mW/cm2, on the dopaminergic turnover of NGF-treated PC12 cells. After MMW exposure, both intracellular and extracellular contents of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were studied using high performance liquid chromatography. Impact of exposure on the dopamine transporter (DAT) expression was also assessed by immunocytochemistry. We analyzed the dopamine turnover by assessing the ratio of DOPAC to DA, and measuring DOPAC accumulation in the medium. Neither dopamine turnover nor DAT protein expression level were impacted by MMW exposure. However, extracellular accumulation of DOPAC was found to be slightly increased, but not significantly. This result was related to the thermal effect, and overall, no evidence of non-thermal effects of MMW exposure were observed on dopamine metabolism. © 2017 The Author. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
Journal of Radiation Research

hal-01580502
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01580502
DOI : 10.1093/jrr/rrx004
PUBMED : 28339776