Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration).
ISSN: 2045-2322

Droits : http://creativecommons.org/licenses/by/
hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/file/The%20environmental%20carcinogen-CCBY%20%281%29.pdf
DOI : 10.1038/srep30776

Éditeur(s) : HAL CCSD Consejo Superior de Investigaciones Científicas
Résumé : International audience
The temporal variation in carbon and nitrogen isotopic compositions (noted as δ 13 C and δ 15 N) was investigated in the convict surgeonfish (Acanthurus triostegus) at Moorea (French Polynesia). Over a period of 24 days, juveniles were reared in aquaria and subjected to two different feeding treatments: granules or algae. The dynamics of δ 13 C and δ 15 N in two muscles (the adductor mandibulae complex and the epaxial musculature) having different functions were compared. At the end of experiments, a steady-state isotopic system in each muscle tissue was not reached. Especially for the algal treatment, we found different patterns of variation in isotopic compositions over time between the two muscles. The turnovers of δ 13 C showed opposite trends for each muscle but differences are mitigated by starvation and by the metamorphosis. Our study highlighted that the metabolism of coral reef fish may be subjected to catabolism or anabolism of non-protein precursors at settlement, inducing variation in isotopic compositions that are not linked to diet change. Comparación de la dinámica de variación isotópica en dos músculos de un pez de arrecife de coral durante la fase de asentamiento Resumen: La variación temporal en la composiciones isotópicas del carbono y nitrógeno (δ 13 C y δ 15 N) fue investigada en el pez cirujano Acanthurus triostegus en Moorea (Polinesia Francesa). Durante un período de 24 días, peces juveniles se mantuvieron en acuarios y se sometieron a dos tratamientos de alimentación: gránulos o algas. Se compararon las dinámicas de cambio δ 13 C y δ 15 N en dos músculos con diferentes funciones (complejo aductor mandibular y musculatura epiaxial). Al final de los experimentos, no se alcanzó un sistema isotópico de estado estacionario en ningún tejido. Especialmente para el tratamiento de algas, encontramos distintos patrones de variación en composiciones isotópicas en el tiempo entre los dos músculos. Las variaciones en δ 13 C mostraron tendencias opuestas para cada músculo, pero las diferencias fueron mitigadas por la inanición y la metamorfosis. Nuestro estudio destaca que el metabolismo de los peces de arrecife puede ser sometido a catabolismo o anabolismo por los precursores no proteicos durante el asentamiento, induciendo variación en las composi-ciones isotópicas que no están vinculados al cambio de dieta.
ISSN: 0214-8358

Droits : http://creativecommons.org/licenses/by-nc/
hal-01212253
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253/file/1598-3145-1-PB.pdf
DOI : 10.3989/scimar.04225.31A

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Environmental factors such as pesticides can cause phenotypic changes in various organisms, including mammals. We studied the effects of the widely used herbicide atrazine (ATZ) on meiosis, a key step of gametogenesis, in male mice. METHODS: Gene expression pattern was analysed by Gene-Chip array. Genome-wide mapping of H3K4me3 marks distribution was done by ChIP-sequencing of testis tissue using Illumina technologies. RT-qPCR was used to validate differentially expressed genes or differential peaks. RESULTS: We demonstrate that exposure to ATZ reduces testosterone levels and the number of spermatozoa in the epididymis and delays meiosis. Using Gene-Chip and ChIP-Seq analysis of H3K4me3 marks, we found that a broad range of cellular functions, including GTPase activity, mitochondrial function and steroid-hormone metabolism, are affected by ATZ. Furthermore, treated mice display enriched histone H3K4me3 marks in regions of strong recombination (double-strand break sites), within very large genes and reduced marks in the pseudoautosomal region of X chromosome. CONCLUSIONS: Our data demonstrate that atrazine exposure interferes with normal meiosis, which affects spermatozoa production
ISSN: 1471-2164

hal-01225493
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225493
DOI : 10.1186/s12864-015-2095-y
PUBMED : 26518232

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The shallow water bivalve Codakia orbicularis lives in symbiotic association with a sulfur-oxidizing bacterium in its gills. The endosymbiont fixes CO2 and thus generates organic carbon compounds, which support the host's growth. To investigate the uncultured symbiont's metabolism and symbiont-host interactions in detail we conducted a proteogenomic analysis of purified bacteria. Unexpectedly, our results reveal a hitherto completely unrecognized feature of the C. orbicularis symbiont's physiology: the symbiont's genome encodes all proteins necessary for biological nitrogen fixation (diazotrophy). Expression of the respective genes under standard ambient conditions was confirmed by proteomics. Nitrogenase activity in the symbiont was also verified by enzyme activity assays. Phylogenetic analysis of the bacterial nitrogenase reductase NifH revealed the symbiont's close relationship to free-living nitrogen-fixing Proteobacteria from the seagrass sediment. The C. orbicularis symbiont, here tentatively named `Candidatus Thiodiazotropha endolucinida', may thus not only sustain the bivalve's carbon demands. C. orbicularis may also benefit from a steady supply of fixed nitrogen from its symbiont-a scenario that is unprecedented in comparable chemoautotrophic symbioses.
ISSN: 2058-5276

hal-01545904
https://hal.archives-ouvertes.fr/hal-01545904
DOI : 10.1038/nmicrobiol.2016.193

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair. Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors. Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells. To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments. Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus. It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction. We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair. Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48 h and peaked at 7 days. At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells. Interestingly, aromatase B expression was significantly reduced 48 h and 7 days after the injury, but surprisingly, at 72 h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms. Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish.
ISSN: 0018-506X

inserm-00831715
http://www.hal.inserm.fr/inserm-00831715
DOI : 10.1016/j.yhbeh.2012.04.003
PUBMED : 22521210

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Subcutaneous fat tissues from an indigenous fat-type breed and an intensively-lean selected breed were studied in juvenile pigs. Combining DIGE with bioinformatics and target analyses of key genes, enzymes or terminal routes, this study identifies metabolic and homeostatic processes, response to organic substances, and acute-phase responses as the main pathways whose proteins were regulated in association with adiposity. Breed-related differences in abundance and activities of malic enzyme and glucose-6-phosphate dehydrogenase NADPH-supplying enzymes suggested up-regulation of the lipogenic pathway to dispose for a greater adiposity. Over-abundance in the lipolytic protein carboxylesterase-1 was revealed in fat-type piglets. A panel of pro- and anti-inflammatory proteins such as serpins, had an altered abundance in the fat-type piglets, suggesting adverse consequences of fat accumulation even in early post-weaning stages. Propensity to low-grade inflammation in fat pigs was reinforced by the up-regulation of genes encoding pro-inflammatory cytokines IL6 and TNF-α in these piglets. Differential abundance in annexin-A5 and pericentrin suggested a positive regulation of cell apoptosis in lean piglets. Our results are relevant in the context of data linking the accretion of body lipids to the physiology and pathology of adipose tissue in models other than rodents for a better control of human health and nutrition.
ISSN: 1874-3919

hal-01122161
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122161
PUBMED : 22061664
DOI : 10.1016/j.jprot.2011.10.012

Éditeur(s) : HAL CCSD Frontiers Media
Résumé : International audience
To date 142 species have been described in the Vibrionaceae family of bacteria, classified into seven genera; Aliivibrio, Echinimonas, Enterovibrio, Grimontia, Photobacterium, Salinivibrio and Vibrio. As vibrios are widespread in marine environments and show versatile metabolisms and ecologies, these bacteria are recognized as one of the most diverse and important marine heterotrophic bacterial groups for elucidating the correlation between genome evolution and ecological adaptation. However, on the basis of 16S rRNA gene phylogeny, we could not find any robust monophyletic lineages in any of the known genera. We needed further attempts to reconstruct their evolutionary history based on multilocus sequence analysis (MLSA) and/or genome wide taxonomy of all the recognized species groups. In our previous report in 2007, we conducted the first broad multilocus sequence analysis (MLSA) to infer the evolutionary history of vibrios using nine housekeeping genes (the 16S rRNA gene, gapA, gyrB, ftsZ, mreB, pyrH, recA, rpoA, and topA), and we proposed 14 distinct clades in 58 species of Vibrionaceae. Due to the difficulty of designing universal primers that can amplify the genes for MLSA in every Vibrionaceae species, some clades had yet to be defined. In this study, we present a better picture of an updated molecular phylogeny for 86 described vibrio species and 10 genome sequenced Vibrionaceae strains, using 8 housekeeping gene sequences. This new study places special emphasis on (1) eight newly identified clades (Damselae, Mediterranei, Pectenicida, Phosphoreum, Profundum, Porteresiae, Rosenbergii, and Rumoiensis); (2) clades amended since the 2007 proposal with recently described new species; (3) orphan clades of genomospecies F6 and F10; (4) phylogenetic positions defined in 3 genome-sequenced strains (N418, EX25, and EJY3); and (5) description of V. tritonius sp. nov., which is a member of the “Porteresiae” clade.
ISSN: 1664-302X

hal-01546980
http://hal.upmc.fr/hal-01546980
DOI : 10.3389/fmicb.2013.00414

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Beggiatoaceae, giant sulphur-oxidizing bacteria, are well known to occur in cold and temperatewaters, as well as hydrothermal vents, where they form dense mats on the floor.However, they have never been described in tropical marine mangroves. Here, we describetwo new species of benthic Beggiatoaceae colonizing a marine mangrove adjacent to mangroveroots. We combined phylogenetic and lipid analysis with electron microscopy in orderto describe these organisms. Furthermore, oxygen and sulphide measurements in and exsitu were performed in a mesocosm to characterize their environment. Based on this, two new species, Candidatus Maribeggiatoa sp. and Candidatus Isobeggiatoa sp. inhabiting tropical marine mangroves in Guadeloupe were identified. The species identified as CandidatusMaribeggiatoa group suggests that this genus could harbour a third cluster with organisms ranging from 60 to 120 μm in diameter. This is also the first description of an Isobeggiatoa species outside of Arctic and temperate waters. The multiphasic approach also gives information about the environment and indications for the metabolism of these bacteria. Our study shows the widespread occurrence of members of Beggiatoaceae family and provides new insight in their potential role in shallow-water marine sulphide-rich environments such as mangroves.
ISSN: 1932-6203

hal-01205641
https://hal.univ-antilles.fr/hal-01205641
https://hal.univ-antilles.fr/hal-01205641/document
https://hal.univ-antilles.fr/hal-01205641/file/Beggiatoa%20Plosone2015.pdf
DOI : 10.1371/journal.pone.0117832

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Glioblastoma (GB), the most frequent primary tumor of the central nervous system, remains one of the most lethal human cancers despite intensive researches. Current paradigm in the study of GB has been focused on inter-patient variability and on trying to isolate new classification elements or prognostic factors. Here, using ICPL, a technique for protein relative quantification by mass spectrometry, we investigated protein expression between the four regions of GB on clinically relevant biopsies from 5 patients. We identified 584 non-redundant proteins and 31 proteins were found to be up-regulated in the tumor region compared to the peri-tumoral brain tissue, among which, 24 proteins belong to an interaction network linked to 4 biological processes. The core of this network is mainly constituted of interactions between beta-actin (ACTB) with heat shock proteins (HSP90AA1, HSPA8) and 14-3-3 proteins (YWHAZ, YWHAG, YWHAB). A cluster of three isoforms of the sodium pump α-subunit (ATP1A1, ATP1A2, ATP1A3) was also identified outside this network. The differential expression observed for ACTB and 14-3-3γ was further validated by western blot and/or immunohistochemistry. Our study confirms the identity of previously proposed molecular targets, highlights several functional processes altered in GB such as energy metabolism and synaptic transmission and could thus provide added value to new therapeutic trails.
ISSN: 1874-3919

hal-00877756
https://hal.archives-ouvertes.fr/hal-00877756
DOI : 10.1016/j.jprot.2012.04.034
PUBMED : 22575386

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The parasitic life cycle of Leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. During that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. We investigated the expression of the invertase BfrA in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely Leishmania major, L. donovani and L. braziliensis. Thereafter, we cloned, overexpressed and biochemically characterized this invertase BfrA from L. major, heterologously expressed in both Escherichia coli and L. tarentolae. For all species, expression levels of BfrA mRNA were correlated to the time of the culture and the parasitic stage (promastigotes > amastigotes). BfrA exhibited no activity when expressed as a glycoprotein in L. tarentolae but proved to be an invertase when not glycosylated, yet owing low sequence homology with other invertases from the same family. Our data suggest that BfrA is an original invertase that is located inside the parasite. It is expressed in both parasitic stages, though to a higher extent in promastigotes. This work provides new insight into the parasite sucrose metabolism
ISSN: 0008-6215

hal-01187142
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187142
DOI : 10.1016/j.carres.2015.07.001
PUBMED : 26279524

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Several epidemiologic studies have shown an interactive effect of heavy smoking and heavy alcohol drinking on the development of hepatocellular carcinoma. It has also been recently described that chronic hepatocyte death can trigger excessive compensatory proliferation resulting later in the formation of tumors in mouse liver. As we previously demonstrated that both benzo[a]pyrene (B[a]P), an environmental agent found in cigarette smoke, and ethanol possess similar targets, especially oxidative stress, to trigger death of liver cells, we decided to study here the cellular and molecular mechanisms of the effects of B[a]P/ethanol coexposure on cell death. After an 18-h incubation with 100nM B[a]P, primary rat hepatocytes were supplemented with 50mM ethanol for 5 or 8h. B[a]P/ethanol coexposure led to a greater apoptotic cell death that could be linked to an increase in lipid peroxidation. Plasma membrane remodeling, as depicted by membrane fluidity elevation and physicochemical alterations in lipid rafts, appeared to play a key role, because both toxicants acted with specific complementary effects. Membrane remodeling was shown to induce an accumulation of lysosomes leading to an important increase in low-molecular-weight iron cellular content. Finally, ethanol metabolism, but not that of B[a]P, by providing reactive oxygen species, induced the ultimate toxic process. Indeed, in lysosomes, ethanol promoted the Fenton reaction, lipid peroxidation, and membrane permeabilization, thereby triggering cell death. To conclude, B[a]P exposure, by depleting hepatocyte membrane cholesterol content, would constitute a favorable ground for a later toxic insult such as ethanol intoxication. Membrane stabilization of both plasma membrane and lysosomes might be a potential target for further investigation considering cytoprotective strategies.
ISSN: 0891-5849

hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/file/Cooperative-interaction_final.pdf
PUBMED : 24681337

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Liver X Receptors (LXRs) α and β and the Peroxisome Proliferator-Activated Receptor α (PPARα) are transcription factors that belong to class II nuclear receptors. They drive the expression of genes involved in hepatic lipid homeostasis and therefore are important targets for the prevention and treatment of nonalcoholic fatty liver disease (NAFLD). LXRs and PPARα are regulated by endogenous ligands, oxysterols and fatty acid derived molecules, respectively. In the liver, pharmacological activation of LXRs leads to the over-expression of genes involved in de novo lipogenesis, while PPARα is critical for fatty acid catabolism in nutrient deprivation. Even if these two nuclear receptors seemed to play opposite parts, recent studies have highlighted that PPARα also influence the expression of genes involved in fatty acids synthesis. In this study, we used pharmacological approaches and genetically engineered mice to investigate the cross-talk between LXRs and PPARα in the regulation of genes responsible for lipogenesis. We first investigated the effect of T0901317 and fenofibrate, two synthetic agonists of LXRs and PPARα, respectively. As expected, T0901317 and fenofibrate induce expression of genes involved LXR-dependent and PPARα-dependent lipogenic responses. Considering such overlapping effect, we then tested whether LXR agonist may influence PPARα driven response and vice versa. We show that the lack of PPARα does not influence the effects of T0901317 on lipogenic genes expression. However, PPARα deficiency prevents the up-regulation of genes involved in ω-hydroxylation that are induced by the LXR agonist. In addition, over-expression of lipogenic genes in response to fenofibrate is decreased in LXR knockout mice as well as the expression of PPARα target genes involved in fatty acid oxidation. Altogether, our work provides in vivo evidence for a central interconnection between nuclear receptors that drive hepatic lipid metabolism in response to oxysterol and fatty acids.
ISSN: 0300-9084

inserm-00872582
http://www.hal.inserm.fr/inserm-00872582
DOI : 10.1016/j.biochi.2012.09.028
PUBMED : 23063693

Éditeur(s) : HAL CCSD Vsevolod Gurevich
Résumé : International audience
Chemotherapy is frequently used to treat primary or metastatic cancers, but intrinsic or acquired drug resistance limits its efficiency. Sphingolipids are important regulators of various cellular processes including proliferation, apoptosis, differentiation, angiogenesis, stress, and inflammatory responses which are linked to various aspects of cancer, like tumor growth, neoangiogenesis, and response to chemotherapy. Ceramide, the central molecule of sphingolipid metabolism, generally mediates antiproliferative and proapoptotic functions, whereas sphingosine-1-phosphate and other derivatives have opposing effects. Among the variety of enzymes that control ceramide generation, acid or neutral sphingomyelinases and ceramide synthases are important targets to allow killing of cancer cells by chemotherapeutic drugs. On the contrary, glucosylceramide synthase, ceramidase, and sphingosine kinase are other targets driving cancer cell resistance to chemotherapy. This chapter focuses on ceramide-based mechanisms leading to cancer therapy sensitization or resistance which could have some impacts on the development of novel cancer therapeutic strategies.
Handb Exp Pharmacol

inserm-00871347
http://www.hal.inserm.fr/inserm-00871347
PUBMED : 23563652
DOI : 10.1007/978-3-7091-1511-4_4

Éditeur(s) : HAL CCSD
Résumé : Structure elucidation of unknown compounds has been the task of natural products chemists for a long time and their approach seems to be the most efficient when it comes to identification. Very recently, Kokkotou et al. proposed a work-flow based on an integrative approach for new metabolite identification. This approach, including prediction of 2D NMR HSQC spectra, demonstrated the necessity for implementation of new algorithms leading to the prediction of 2D NMR spectra. Herein we present a method based on both quantum mechanics (QM) and Hierarchical Organisation of Spherical Environments (HOSE) of the prediction 2D NMR spectra.
https://hal.archives-ouvertes.fr/hal-01416667

hal-01416667
https://hal.archives-ouvertes.fr/hal-01416667
https://hal.archives-ouvertes.fr/hal-01416667/document
https://hal.archives-ouvertes.fr/hal-01416667/file/MRC_v1.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Due to their geographic location and traditional diet, rich in seafood and marine mammals, the Inuit living in Arctic Quebec are exposed to high amounts of pollutants, including organochlorine pesticides (OCPs). While the adverse developmental effects of these pesticides on child cognitive functions are well known, the effects of developmental exposure to OP on sensory processes have not been investigated. The aim of this longitudinal study was to assess the effects of prenatal and childhood exposure to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its major metabolite 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), on visual processing in Inuit children in Nunavik (Arctic Québec). p,p'-DDT and p,p'-DDE concentrations were determined from umbilical cord and 5- and 11-year plasma samples. Visual evoked potentials (VEPs) were successfully recorded in 150 children at 4 contrast levels (95%, 30%, 12%, and 4%). Hierarchical multiple regressions were conducted to determine the association between p,p'-DDT, or p,p'-DDE, exposure and VEPs while controlling for the effects of various confounders, including fish nutrients and other contaminants. p,p'-DDE measured in umbilical cord plasma was significantly related to the amplitude of the N150 response at the lowest contrast (4%). In addition, 5-year p,p'-DDE plasma concentration was significantly associated with decreased N75 amplitude. These findings indicate that p,p'-DDE exposure, both pre- and postnatally, during early childhood is associated with visual processing impairment later in life.
ISSN: 0161-813X

hal-01061309
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309/file/Prenatal_and_5-year-NEUTOX-D-13-00192R2_v4.pdf
DOI : 10.1016/j.neuro.2014.04.009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Sphingolipids, in particular ceramide, have been described as important components of cellular signalling pathways. Ceramide can be produced via multiple mechanisms including through the hydrolysis of sphingomyelin by acid and neutral sphingomyelinase or by a de novo synthesis pathway. Recent studies have identified sphingomyelinases and ceramide synthases as important targets for γ-irradiation and chemotherapeutic drugs. Likewise, common cancer treatment modalities, such as γ-irradiation and many chemotherapeutic agents, induce cell death via the generation of ceramide. This suggests that the manipulation of ceramide production and metabolism could offer promising a means for the enhancement of anti-tumor therapies. The focus of this mini-review will be to discuss contemporary evidence suggesting that ceramide forming pathways and ceramide itself are important targets for the treatment of tumors and the development of novel tumor treatment strategies.
ISSN: 0304-3835

hal-00682458
https://hal.archives-ouvertes.fr/hal-00682458
DOI : 10.1016/j.canlet.2011.07.010
PUBMED : 21862212

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cnidarian-dinoflagellate symbiosis mainly relies on nutrient recycling, thus providing both partners with a competitive advantage in nutrient-poor waters. Essential processes related to lipid metabolism can be influenced by various factors, including hyperthermal stress. This can affect the lipid content and distribution in both partners, while contributing to symbiosis disruption and bleaching. In order to gain further insight into the role and distribution of lipids in the cnidarian metabolism, we investigated the lipid composition of the sea anemone Anemonia viridis and its photosynthetic dinoflagellate endosymbionts (Symbiodinium). We compared the lipid content and fatty acid profiles of the host cellular layers, non-symbiotic epidermal and symbiont-containing gastrodermal cells, and those of Symbiodinium, in a mass spectrometry-based assessment. Lipids were more concentrated in Symbiodinium cells, and the lipid class distribution was dominated by polar lipids in all tissues. The fatty acid distribution between host cell layers and Symbiodinium cells suggested potential lipid transfers between the partners. The lipid composition and distribution was modified during short-term hyperthermal stress, mainly in Symbiodinium cells and gastrodermis. Exposure to elevated temperature rapidly caused a decrease in polar lipid C18 unsaturated fatty acids and a strong and rapid decrease in the abundance of polar lipid fatty acids relative to sterols. These lipid indicators could therefore be used as sensitive biomarkers to assess the physiology of symbiotic cnidarians, especially the effect of thermal stress at the onset of cnidarian bleaching. Overall, the findings of this study provide some insight on key lipids that may regulate maintenance of the symbiotic interaction.
ISSN: 1095-6433

hal-01546160
https://hal.archives-ouvertes.fr/hal-01546160
DOI : 10.1016/j.cbpa.2015.10.017

Éditeur(s) : HAL CCSD IWA Publishing
Résumé : International audience
The widely occurring degradation product aminomethylphosphonic acid (AMPA) is a result of glyphosate and amino-polyphosphonate degradation. Massive use of the parent compounds leads to the ubiquity of AMPA in the environment, and particularly in water. The purpose of this review is to summarize and discuss current insights into AMPA formation, transport, persistence and toxicity. In agricultural soils, AMPA is concentrated in the topsoil, and degrades slowly in most soils. It can reach shallow groundwater, but rarely managed to enter deep groundwater. AMPA is strongly adsorbed to soil particles and moves with the particles towards the stream in rainfall runoff. In urban areas, AMPA comes from phosphonates and glyphosate in wastewater. It is commonly found at the outlets of Wastewater Treatment Plants (WWTP). Sediments tend to accumulate AMPA, where it may be biodegraded. Airborne AMPA is not negligible, but does wash-out with heavy rainfall. AMPA is reported to be persistent and can be biologically degraded in soils and sediments. Limited photodegradation in waters exists. AMPA mainly has its sources in agricultural leachates, and urban wastewater effluents. The domestic contribution to urban loads is negligible. There is a critical lack of epidemiological data - especially on water exposure - to understand the toxicological effects, if any, of AMPA on humans. Fortunately, well operated water treatment plants remove a significant proportion of the AMPA from water, even though there are not sufficient regulatory limits for metabolites.
ISSN: 0043-1354

hal-01516026
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01516026
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01516026/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01516026/file/Grandcoin%20et%20al.%20-%20AminoMethylPhosphonic%20acid%20%28AMPA%29%20in%20natural%20water.pdf
DOI : 10.1016/j.watres.2017.03.055

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.
ISSN: 0268-1161

inserm-00866016
http://www.hal.inserm.fr/inserm-00866016
PUBMED : 23670170
DOI : 10.1093/humrep/det112