Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor. They have potentially therapeutic actions in breast cancer by reducing the proliferation of cancer cells. However, the molecular mechanisms driving these effects remain elusive. METHODS: First, to determine the proliferative or anti-proliferative effects of glyceollins, in vivo and in vitro approaches were used. The length of epithelial duct in mammary gland as well as uterotrophy after treatment by E2 and glyceollins and their effect on proliferation of different breast cell line were assessed. Secondly, the ability of glyceollin to activate ER was assessed by luciferase assay. Finally, to unravel molecular mechanisms involved by glyceollins, transcriptomic analysis was performed on MCF-7 breast cancer cells. RESULTS: In this study, we show that synthetic versions of glyceollin I and II exert anti-proliferative effects in vivo in mouse mammary glands and in vitro in different ER-positive and ER-negative breast cell lines. Using transcriptomic analysis, we produce for the first time an integrated view of gene regulation in response to glyceollins and reveal that these phytochemicals act through at least two major pathways. One pathway involving FOXM1 and ERα is directly linked to proliferation. The other involves the HIF family and reveals that stress is a potential factor in the anti-proliferative effects of glyceollins due to its role in increasing the expression of REDD1, an mTORC1 inhibitor. CONCLUSION: Overall, our study clearly shows that glyceollins exert anti-proliferative effects by reducing the expression of genes encoding cell cycle and mitosis-associated factors and biomarkers overexpressed in cancers and by increasing the expression of growth arrest-related genes. These results reinforce the therapeutic potential of glyceollins for breast cancer.
ISSN: 1478-811X

hal-01560288
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560288
DOI : 10.1186/s12964-017-0182-1
PUBMED : 28666461

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Plant responses to natural enemies include formation of secondary metabolites acting as direct or indirect defenses. Volatile terpenes represent one of the most diverse groups of secondary metabolites. We aimed to explore evolutionary patterns of volatile terpene emission. We measured the composition of damage-induced volatile terpenes from 202 Amazonian tree species, spanning the angiosperm phylogeny. Volatile terpenes were extracted with solid-phase micro extraction and desorbed in a gas chromatography–mass spectrometry for compound identification. The chemical diversity of the terpene blend showed a strong phylogenetic signal as closely related species emitted a similar number of compounds. Closely related species also tended to have compositionally similar blends, although this relationship was weak. Meanwhile, the ability to emit a given compound showed no significant phylogenetic signal for 200 of 286 compounds, indicating a high rate of diversification in terpene synthesis and/or great variability in their expression. Three lineages (Magnoliales, Laurales, and Sapindales) showed exceptionally high rates of terpene diversification. Of the 70 compounds found in >10% of their species, 69 displayed significant correlated evolution with at least one other compound. These results provide insights into the complex evolutionary history of volatile terpenes in angiosperms, while highlighting the need for further research into this important class of compounds.
ISSN: 2045-7758

Droits : http://creativecommons.org/licenses/by/
hal-01296640
http://hal.upmc.fr/hal-01296640
http://hal.upmc.fr/hal-01296640/document
http://hal.upmc.fr/hal-01296640/file/ece31810.pdf
DOI : 10.1002/ece3.1810

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences
Résumé : International audience
BACKGROUND: Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function. OBJECTIVE: To study the relation between women's exposure to glycol ethers and time to pregnancy. METHODS: Urine from randomly selected women in the PELAGIE mother-child cohort who had samples collected before 19 weeks of gestation was tested to measure eight glycol ether metabolites by chromatography coupled to mass spectrometry. Time to pregnancy was collected at the beginning of the pregnancy by asking women how many months they took to conceive. Associations between metabolite levels and time to pregnancy were estimated in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders. RESULTS: Glycol ether metabolites were detected in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy (fecundability OR 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (≥1.38 mg/L) vs. first-quartile concentration (<0.14 mg/L)). This association remained stable after multiple sensitivity analyses. CONCLUSION: Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but may also be surrogates for potential co-exposures frequently present in cosmetics.
ISSN: 0091-6765

hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/file/Urinary_Glycol_Ether-accepted.pdf
DOI : 10.1289/ehp.1206103

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
Chemical mediation regulates behavioral interactions between species and thus affects population structure,community organization and ecosystem function. Among marine taxa that have developed chemicalmediation strategies, gastropods belong to a diverse group of molluscs found worldwide, including specieswith a coiled, reduced or absent shell. Most gastropods use natural products to mediate a wide range ofbehaviors such as defense, prey location or interactions with con- and hetero-geners. Their chemicallydefended diet, such as cyanobacteria, algae, sponges, bryozoans and tunicates, provides them witha considerable opportunity either as shelter from predators, or as a means to enhance their own chemicaldefense. In addition to improving their defenses, molluscs also use prey secondary metabolites in complexchemical communication including settlement induction, prey detection and feeding preferences. Theassimilation of prey secondary metabolites further provides the opportunity for interactions withconspecifics via diet-derived chemical cues or signals. This review intends to provide an overview on thesequestration, detoxification, and biotransformation of diet-derived natural products, as well as the role ofthese compounds as chemical mediators in gastropod-prey interactions.
ISSN: 0265-0568

hal-01563402
https://hal-univ-perp.archives-ouvertes.fr/hal-01563402
DOI : 10.1039/c6np00097e

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Extractives that provide natural resistance to Bagassa guianensis Aubl. heartwood were examined. Soil-bed tests showed that the B. guianensis heartwood resistance was significantly reduced after ethyl acetate extraction, whereas methanol and especially water extractions improved the resistance. The ethyl acetate extract was submitted to a bioguided fractionation, and fractions were tested against one wood-destroying fungal strain (Pycnoporus sanguineus) and two human pathogenic fungal strains (Candida glabrata (yeast) and Trichophyton rubrum (filamentous dermatophyte)). Fraction F7, which exhibited the strongest antifungal activity, was subsequently fractionated by high performance liquid chromatography (HPLC). Six previously described compounds were isolated. Although the two moracins, 6-O-methyl-moracin N (3) and moracin N (4) were the most active against fungal strains with MIC values between 4 and 16 μg ml−1, the isolated compounds showed less or equivalent antifungal activity than the initial fraction. Possible synergism between compounds 3 and 4 and other secondary metabolites have been hypothesized. Our study demonstrated that this extract as a whole might be used as a wood preservation or antimycotic product.
International Biodeterioration and Biodegradation

hal-00694532
https://hal.archives-ouvertes.fr/hal-00694532
DOI : 10.1016/j.ibiod.2011.10.016

Éditeur(s) : HAL CCSD Elsevier
Résumé : Eperua falcata (Aublet), a late-successional species in tropical rainforest and one of the most abundant tree in French Guiana, has developed an original strategy concerning N-acquisition by largely preferring nitrate, rather than ammonium (H. Schimann, S. Ponton, S. Hattenschwiler, B. Ferry, R. Lensi, A.M. Domenach, J.C. Roggy, Differing nitrogen use strategies of two tropical rainforest tree species in French Guiana: evidence from N-15 natural abundance and microbial activities, Soil Biol, Biochem. 40 (2008) 487-494). Given the preference of this species for nitrate, we hypothesized that root exudates would promote nitrate availability by (a) enhancing nitrate production by stimulating ammonium oxidation or (b) minimizing nitrate losses by inhibiting denitrification. Root exudates were collected in situ in monospecific planted plots. The phytochemical analysis of these exudates and of several of their corresponding root extracts was achieved using UHPLC/DAD/ESI-QTOF and allowed the identification of diverse secondary metabolites belonging to the flavonoid family. Our results show that (i) the distinct exudation patterns observed are related to distinct root morphologies, and this was associated with a shift in the root flavonoid content, (ii) a root extract representative of the diverse compounds detected in roots showed a significant and selective metabolic inhibition of isolated denitrifiers in vitro, and (iii) in soil plots the abundance of nirK-type denitrifiers was negatively affected in rhizosphere soil compared to bulk. Altogether this led us to formulate hypothesis concerning the ecological role of the identified compounds in relation to N-acquisition strategy of this species. (C) 2013 Elsevier Masson SAS. All rights reserved.
ISSN: 0981-9428

hal-01032437
https://hal.archives-ouvertes.fr/hal-01032437
DOI : 10.1016/j.plaphy.2013.05.003

Éditeur(s) : HAL CCSD Elsevier
Résumé : Volatile terpenes are among the most diverse class of defensive compounds in plants, and they are implicated in both direct and indirect defense against herbivores. In terpenes, both the quantity and the diversity of compounds appear to increase the efficiency of defense as a diverse blend of compounds provides a more efficient protection against a broader range of herbivores and limits the chances that an enemy evolves resistance. Theory predicts that plant defensive compounds should be allocated differentially among tissues according to the value of the tissue, its cost of construction and the herbivore pressure on it. We collected volatile terpenes from bark and leaves of 178 individual tree belonging to 55 angiosperm species in French Guiana and compare the kind, amount, and diversity of compounds in these tissues. We hypothesized that in woody plants, the outermost part of the trunk should hold a more diverse blend of volatile terpenes. Additionally, as herbivore communities associated with the leaves is different to the one associated with the bark, we also hypothesized that terpene blends should be distinct in the bark vs. the leaves of a given species. We found that the mixture of volatile terpenes released by bark is different and more diverse than that released by leaves, both in monoterpenes and sesquiterpenes. This supports our hypothesis and further suggests that the emission of terpenes by the bark should be more important for trunk defense than previously thought. (c) 2012 Elsevier Ltd. All rights reserved.
ISSN: 0031-9422

hal-01032417
https://hal.archives-ouvertes.fr/hal-01032417
DOI : 10.1016/j.phytochem.2012.07.003

Résumé : Aujourd’hui, il est indispensable de découvrir de nouveaux agents thérapeutiques pour faire face à l’expansion des infections fongiques humaines. D’un autre côté, certains arbres amazoniens ont acquis des moyens pour se protéger contre la dégradation fongique. Ces composés d’origine végétale pourraient donc être des candidats potentiels au développement de composés antifongiques. Il est ainsi exposé dans ce travail la sélection bio-inspirée et la récolte d’espèces d’arbres amazoniens résistants à la dégradation fongique ; à partir desquelles il est proposé d’isoler, d’identifier et de valoriser les métabolites responsables de la durabilité naturelle et d’étudier leurs propriétés sur des champignons pathogènes humains. Cette étude a conduit à l’isolement de molécules inédites apportant un complément d’information chimiotaxonomique pour les espèces étudiées. De plus, il a pu être mis en avant deux molécules pouvant devenir des composés pertinents pour le développement de traitements antimycotiques.
It is now essential to discover new therapeutic agents against the increase of human fungal infections. On the other hand, some Amazonian trees have succeeded to develop a chemical defense arsenal to protect themselves against fungal degradation. These compounds of plant origin could become potential candidates for the development of antifungal compounds for the treatment of human fungal diseases. Therefore, this manuscript describes the bio-inspired selection and collection of Amazonian tree species capable of specializing a highly fungiresistant wood; from which it is proposed to isolate, identify and valorize the secondary metabolites responsible for the natural durability, and study their properties on human pathogenic fungi. Ultimately, this study led to the isolation of new compounds and providing additional important chemotaxonomic information for the species studied. In addition, it as been established that two compounds could be relevant for the development of antimitotic therapies.

http://www.theses.fr/2011AGUY0467/document

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes. Sponges' self defence mechanisms involving dialogue molecules thus represent a pertinent research track for potent anti-infective and anti-biofilm activities such as quorum sensing inhibitors (QSIs). The investigation of the QSI crude extract of Leucetta chagosensis Dendy, 1863 led to the isolation of three new alkaloids, isonaamine D, di-isonaamidine A and leucettamine D, along with the known isonaamine A and isonaamidine A. Isonaamidine A and isonaamine D were identified as inhibitors of the three quorum sensing pathways of Vibrio harveyi (CAI-1, AI-2 and harveyi auto inducer), but isonaamidine A displayed the strongest activity on AI-2 biosensor. Both compounds are new examples of natural QSIs of V. harveyi. These results outline the importance of these secondary metabolites for their producing organisms themselves in their natural environment, as well as the potential of the marine resource for aquaculture needs.
ISSN: 0266-8254

hal-01684926
https://hal.archives-ouvertes.fr/hal-01684926
DOI : 10.1111/lam.12461
PUBMED : 26138555

Résumé : Dans le cadre de la promotion de systèmes de culture alternatifs à moindres intrants chimiques, des études sur l'introduction de plantes de service ayant vocation à réduire l'usage des pesticides et engrais azotés mobilisent un effort de recherche considérable. Dans le cadre de la production bananière pour laquelle la nuisibilité causée par les nématodes phytoparasites constitue l'une des principales contraintes, une des principales alternatives à l'utilisation de nématicides chimiques repose sur l'usage raisonné en rotation ou en association culturale de plantes de service à propriétés nématorégulatrices. Parmi les espèces candidates, celles du genre Crota/aria spp. ont largement été étudiées en raison de leur aptitude à contrôler les nématodes phytoparasites. Une méta-analyse révèle cependant que même si de nombreux auteurs s'accordent à reconnaître les propriétés allélopathiques des plantes de cette espèce, ils sont également enclins à reconnaître la forte variabilité d'expression de ces propriétés vis-à-vis du contrôle des nématodes selon les situations expérimentées. L'objectif de ce travail repose sur la compréhension du déterminisme biochimique des exsudats. La stratégie expérimentale mise en oeuvre a consisté à tester en conditions contrôlées le comportement biochimique des exsudats racinaires de deux espèces de crotalaires (C retusa, C spectabilis) et d'une espèce sensible, le bananier dessert (Musa spp.) en fonction i) de conditions biotiques variées -i.e. présence ou non de nématodes (Radopholus similis et Meloidogyne arenariaï, et présence ou non de mycorhizes-, ii) de conditions abiotiques contrastées -i.e. utilisation d'un sol naturel vs. substrat neutre, ajout ou non d'engrais chimique. La méthodologie innovante des «plantes à traire » (Brevet INRA) a été requise pour pouvoir travailler sur les exsudats racinaires des plantes conditionnées plutôt que sur des Iixiviats, comme réalisé dans des expérimentations antérieures.Les résultats obtenus en spectrophométrie visible montrent que la modification des conditions abiotiques affecte de manière importante les profils biochimiques des plantes étudiées. En présence du nématode 1..·1. arenaria les profils biochimiques des deux crotalaires sont également modifiés. Des biotests réalisés à l'aide des exsudats racinaires conditionnés au préalable par les modifications biotiques ont permis de démontrer l'effet nématostatique des crotalaires. Des analyses biochimiques en Ge-MS mettent en évidence de manière plus précise des molécules actives mises en jeu sous différentes modalités biotiques et abiotiques. Ces recherches, de portée générique, permettront de mieux comprendre les conditions de l'environnement qui régulent les profils biochimiques des exsudats racinaires des crotalaires et par extension, seront applicables aux recherches menées sur d'autres plantes de service candidates. Ceci aidera, à terme, à définir les conditions environnementales à réunir, pour orienter de manière optimale les effets allélopathiques dans une perspective de nématorégulation naturelle
As part of the promotion of alternative cropping systems at lower chemical inputs, studies on the introduction of cover crops designed to reduce the use of pesticides and nitrogen fertilizers mobilize a considerable research effort. Under banana production for which the hannfu1ness caused by plant-parasitic-nematodes is one ofthe main constraints, one of the main alternatives to the use ofchemical nematicides is based on the rational use in rotation or intercropping of cover rI crops to proteet crops from plant-parasitic-nematodes, Among the candidate species, the species from the genus of Crota/aria spp. have been widely studied because of their ability to control plant parasitic-nematodes. A meta-analysis reveals that although many authors agree allelopathic properties of these species, they are also likely to recognize the high variability of expression of these properties vis-àvis the control of nematodes according to the situations experieaced.. The objective of this woIk is focnsed on the onderstanding of the biochemical determinism of mot exudates onder environment biotic and abiotic variations. The experimental strategy was 10 test onder controlled conditions the biochemical behavior of mot exudates of two species of crotalarias (C retusa, C. spectabilis) and a susceptible species, the dessert banana crop (Musa spp.) with i) modification ofbiotic conditions -ie presence or absence of nematodes iMeloidogyne arenaria and Radopho/us similis), and presence or absence of mycorrhiza-ii) contrasting abiotic conditions -ie using a natural soil vs. neutral substrate, whether to add fertilizer. The innovative methodology of "milking plants" (patent INRA) was required in order to work on the root exudates of plants packed rather thanleachate, as done in previous experiments. The results obtained show that 'visible spectrophotometry changing abiotic conditions affect significantly the biochemical profiles of the studied plants. In the presence of nematode M. arenaria biochemical profiles of both crotalarias are also changed. Bioassays conducted using mot exudates conditioned in advance by biotic changes have demonstrated the effect of nématostatique crotalarias. Biochemical Ge-MS demonstrate more clearly active molecules that are involved in varions biotic and abiotic conditions. This research, generic scope, to better understand the environmental conditions that regulate biochemical profiles of mot exudates crotalarias and by extension, will apply to research on other plants service candidates. This will ultimately define the environmental conditions to meet, to guide optimal allelopathic effects from the perspective ofnatural nématorégulation

http://www.theses.fr/2012AGUY0561/document