Inflammatory Pathway Genes Belong to Major Targets of Persistent Organic Pollutants in Adipose Cells

Background: Epidemiological studies emphasize the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT)

The AhR twist: ligand-dependent AhR signaling and pharmaco-toxicological implications

International audienceThe aryl hydrocarbon receptor (AhR) is a transcription factor which is activated by diverse compounds and regulates the expression of xenobiotic metabolism genes. Recent studies have unraveled unsuspected physiological roles and novel alternative ligand-specific pathways for this receptor. In this review, we discuss these novel aspects and focus on the different responses elicited by the diverse endogenous and/or exogenous AhR ligands. In addition to challenging the relevance of the 'agonist/antagonist' classification of ligands, we introduce the concept of AhR plasticity as a primordial factor in the generation of these pathways. Finally, we suggest several promising perspectives for the pharmacological modulation of these responses

New insigths on the metabolic diversity among the epibiotic microbial community of the hydrothermal shrimp Rimicaris exoculata

En libre-accès sur Archimer : http://archimer.ifremer.fr/doc/2008/publication-4563.pdfInternational audienceThe Rimicaris exoculata dominates the megafauna of some of the Mid Atlantic ridge hydrothermal vent sites. This species harbors a rich community of bacterial epibionts inside its gill chamber. Literature data indicate that a single 16S rRNA phylotype dominates this epibiotic community, and is assumed to be a sulfide-oxidizing bacteria. However attempts of cultivation were not successful and did not allow to confirm it. The aim of our study was to test the hypothesis of sulfide oxidation in the gill chamber, by a multidisciplinary approach, using in vivo experiments at in situ pressure in the presence of sulfide, microscopic observations and a molecular survey. Morphology of microorganisms, before and after treatment, was analyzed to test the effect of sulfide depletion and re-exposure. Our observations, as well as molecular data indicate a wider diversity than previously described for this shrimp's epibiotic community. We observed occurrence of bacterial intracellular sulfur- and iron-enriched granules and some methanotrophic-like bacteria cells for the first time. Genes that are characteristic of methane- oxidizing (pmoA) and sulfide-oxidizing (APS) bacteria were identified. These results suggest that three metabolic types (iron, sulfide and methane oxidation) may co-occur within the epibiont community associated with Rimicaris exoculata. As this shrimp colonizes chemically contrasted environments, the relative abundance of each metabolic type could vary according to the local availability of reduced compounds

TM6F2-T and PNPLA3-G genetic variants co-modulate the risk of hepatocellular carcinoma in caucasian patients with alcoholic cirrhosis. Inter-cohort validation in 1068 patients.

0info:eu-repo/semantics/publishe

Identification of a new stilbene-derived inducer of paraoxonase 1 and ligand of the Aryl hydrocarbon Receptor.

International audienceParaoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme, synthesized in the liver and secreted into the blood. PON1 displays antioxidant properties and is involved in organophosphorous compounds and oxidized lipids degradation. Because of these beneficial effects, pharmacological regulation of PON1 appears to be highly relevant in toxicology and cardiology. Recent studies undertaken on the regulation of the PON1 promoter in our laboratory have identified resveratrol, through its activation of the Aryl hydrocarbon Receptor (AhR), as a putative inducer of PON1. We have tested a new modulator of AhR, (Z)-2,3-bis (4-nitrophenyl)-acrylonitrile, and established that it is a more potent inducer of PON1 at the mRNA, protein and enzymatic activity as compared to resveratrol. It also acts by activating the AhR. However, in contrast with traditional AhR agonists, it does not induce cyp1A1 transcription. (Z)-2,3-bis (4-nitrophenyl)-acrylonitrile is therefore a specific AhR modulator targeting PON1

PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis.

LetterFLWINSCOPUS: le.jinfo:eu-repo/semantics/publishe

Seaweed Habitats on the Shore: Characterization through Hyperspectral UAV Imagery and Field Sampling

Intertidal macroalgal habitats are major components of temperate coastal ecosystems. Their distribution was studied using field sampling and hyperspectral remote mapping on a rocky shore of Porspoder (western Brittany, France). Covers of both dominating macroalgae and the sessile fauna were characterized in situ at low tide in 24 sampling spots, according to four bathymetric levels. A zone of ca. 17,000 m2 was characterized using a drone equipped with a hyperspectral camera. Macroalgae were identified by image processing using two classification methods to assess the representativeness of spectral classes. Finally, a comparison of the remote imaging data to the field sampling data was conducted. Seven seaweed classes were distinguished by hyperspectral pictures, including five different species of Fucales. The maximum likelihood (MLC) and spectral angle mapper (SAM) were both trained using image-derived spectra. MLC was more accurate to classify the main dominating species (Overall Accuracy (OA) 95.1%) than SAM (OA 87.9%) at a site scale. However, at sampling points scale, the results depend on the bathymetric level. This study evidenced the efficiency and accuracy of hyperspectral remote sensing to evaluate the distribution of dominating intertidal seaweed species and the potential for a combined field/remote approach to assess the ecological state of macroalgal communities

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

International audienceInduction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and-4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2-or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression OPEN ACCESS Mar. Drugs 2015, 13 6589 significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases

Activation of the aryl hydrocarbon receptor by carcinogenic aromatic amines and modulatory effects of their N-acetylated metabolites

International audienceAromatic amines (AAs) are an important class of chemicals which account for 12 % of known carcinogens. The biological effects of AAs depend mainly on their biotransformation into reactive metabolites or into N-acetylated metabolites which are generally considered as less toxic. Although the activation of the aryl hydrocarbon receptor (AhR) pathway by certain carcinogenic AAs has been reported, the effects of their N-acetylated metabolites on the AhR have not been addressed. Here, we investigated whether carcinogenic AAs and their N-acetylated metabolites may activate/modulate the AhR pathway in the absence and/or the presence of a bona fide AhR ligand (benzo[a]pyrene/B(a)P]. In agreement with previous studies, we found that certain AAs activated the AhR in human liver and lung cells as assessed by an increase in cytochrome P450 1A1 (CYP1A1) expression and activity. Altogether, we report for the first time that these properties can be modulated by the N-acetylation status of the AA. Whereas 2-naphthylamine significantly activated the AhR and induced CYP1A1 expression, its N-acetylated metabolite was less efficient. In contrast, the N-acetylated metabolite of 2-aminofluorene was able to significantly activate AhR, whereas the parent AA, 2-aminofluorene, did not. In the presence of B(a)P, activation of AhR or antagonist effects were observed depending on the AA or its N-acetylated metabolite. Activation and/or modulation of the AhR pathway by AAs and their N-acetylated metabolites may represent a novel mechanism contributing to the toxicological effects of AAs. More broadly, our data suggest biological interactions between AAs and other classes of xenobiotics through the AhR pathway