11 results on '"Juricek L"'
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2. Uneinterpretation géométrique des contraintes d'état dans les processus optimaux
- Author
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Bonnemay, A., primary and Bonnemay-Juricek, L., additional
- Published
- 1970
- Full Text
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3. Geometry of Pareto equilibria and a maximum principle in N-person differential games
- Author
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Blaquiere, A, Juricek, L, and Wiese, K.E
- Published
- 1972
- Full Text
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4. Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling.
- Author
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Watzky M, Huard S, Juricek L, Dairou J, Chauvet C, Coumoul X, Letessier A, and Miotto B
- Subjects
- Animals, Humans, Mice, Promoter Regions, Genetic, Signal Transduction, Xenobiotics, Hexokinase genetics, Hexokinase metabolism, Hexokinase pharmacology, Receptors, Aryl Hydrocarbon genetics, Receptors, Aryl Hydrocarbon metabolism
- Abstract
The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression of HK2 is positively regulated by AHR upon exposure to agonists both in human cells and in mice lung tissues. Conversely, over-expression of HK2 regulates the abundance of many proteins involved in the regulation of AHR signalling and these changes are linked with altered AHR expression levels and transcriptional activity. HK2 expression also shows a negative correlation with AHR promoter methylation in tumours, and these tumours with high HK2 expression and low AHR methylation are associated with a worse overall survival in patients. In sum, our study provides novel insights into how AHR signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2022
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5. Age-dependent vulnerability of the ovary to AhR-mediated TCDD action before puberty: Evidence from mouse models.
- Author
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Devillers MM, Petit F, Giton F, François CM, Juricek L, Coumoul X, Magre S, Cohen-Tannoudji J, and Guigon CJ
- Subjects
- Animals, Cytochrome P-450 CYP1A1 metabolism, Endocrine Disruptors metabolism, Estradiol metabolism, Estrogens pharmacology, Female, Granulosa Cells drug effects, Ligands, Mice, Mice, Inbred C57BL, Ovary drug effects, Polychlorinated Dibenzodioxins metabolism, Sexual Maturation drug effects, Signal Transduction drug effects, Ovary physiology, Polychlorinated Dibenzodioxins toxicity, Receptors, Aryl Hydrocarbon metabolism
- Abstract
In female mammals, puberty and fertility are regulated by the synthesis of estradiol (E2) by the ovaries at the infantile stage and at the approach of puberty, a process which may be affected by endocrine disrupting chemicals (EDC)s acting through the Aryl hydrocarbon receptor (AhR). However, there is no information on AhR-mediated regulation of ovarian estrogenic activity during these developmental periods. Here, we assessed in mouse models, the intrinsic and exogenous ligand-induced AhR action on E2 synthesis at the infantile stage (14 days postnatal (dpn)) and at the approach of puberty (28 dpn). Intrinsic AhR pathway became activated in the ovary at the approach of puberty, as suggested by the decreased intra-ovarian expression in prototypical and steroidogenesis-related AhR targets and E2 contents in Ahr knockout (Ahr
-/- ) mice versus Ahr+/+ mice exclusively at 28 dpn. Accordingly, AhR nuclear localization in granulosa cells, reflecting its activity in cells responsible for E2 synthesis, was much lower at 14 dpn than at 28 dpn in C57BL/6 mice. However, AhR signaling could be activated by exogenous ligands at both ages, as revealed by FICZ- and TCDD-induced Ahrr and Cyp1a1 expression in C57BL/6 mice. Nevertheless, TCDD impacted ovarian estrogenic activity only at 28 dpn. This age-related AhR action may be ligand-dependent, since FICZ had no effect on E2 synthesis at 28 dpn. In conclusion, AhR would not regulate ovarian estrogenic activity before the approach of puberty. Its activation by EDCs may be more detrimental to reproductive health at this stage than during infancy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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6. The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial.
- Author
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Coumoul X, Servien R, Juricek L, Kaddouch-Amar Y, Lippi Y, Berthelot L, Naylies C, Morvan ML, Antignac JP, Desdoits-Lethimonier C, Jegou B, Tremblay-Franco M, Canlet C, Debrauwer L, Le Gall C, Laurent J, Gouraud PA, Cravedi JP, Jeunesse E, Savy N, Dandere-Abdoulkarim K, Arnich N, Fourès F, Cotton J, Broudin S, Corman B, Moing A, Laporte B, Richard-Forget F, Barouki R, Rogowsky P, and Salles B
- Subjects
- Animal Feed standards, Animals, Consumer Product Safety, Edible Grain genetics, Female, Food, Genetically Modified standards, Male, Plants, Genetically Modified genetics, Rats, Rats, Wistar, Toxicity Tests methods, Zea mays chemistry, Animal Feed toxicity, Edible Grain chemistry, Food, Genetically Modified toxicity, Plants, Genetically Modified chemistry, Zea mays genetics
- Abstract
The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial. Rats were necropsied after 3 and 6 months. Based on the Organization for Economic Cooperation and Development test guideline 408, the parameters tested showed a limited number of significant differences in pairwise comparisons, very few concerning GMP versus non-GMP. In such cases, no biological relevance could be established owing to the absence of difference in biologically linked variables, dose-response effects, or clinical disorders. No alteration of the reproduction function and kidney physiology was found. Metabolomics analyses on fluids (blood, urine) were performed after 3, 4.5, and 6 months. Transcriptomics analyses on organs (liver, kidney) were performed after 3 and 6 months. Again, among the significant differences in pairwise comparisons, no GMP effect was observed in contrast to that of maize variety and culture site. Indeed, based on transcriptomic and metabolomic data, we could differentiate MON- to NK-based diets. In conclusion, using this experimental design, no biomarkers of adverse health effect could be attributed to the consumption of GMP diets in comparison with the consumption of their near-isogenic non-GMP controls., (© The Author 2018. Published by Oxford University Press on behalf of the Society of Toxicology.)
- Published
- 2019
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7. The Aryl Hydrocarbon Receptor and the Nervous System.
- Author
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Juricek L and Coumoul X
- Subjects
- Animals, Behavior, Animal, Blood-Brain Barrier metabolism, Cell Differentiation, Cell Proliferation, Cell Survival, Endocrine Disruptors pharmacology, Gene Expression Regulation drug effects, Humans, Ligands, Nervous System drug effects, Neurogenesis drug effects, Neurosecretory Systems drug effects, Neurosecretory Systems physiology, Neurotransmitter Agents metabolism, Vertebrates, Nervous System metabolism, Receptors, Aryl Hydrocarbon genetics, Receptors, Aryl Hydrocarbon metabolism
- Abstract
The aryl hydrocarbon receptor (or AhR) is a cytoplasmic receptor of pollutants. It translocates into the nucleus upon binding to its ligands, and forms a heterodimer with ARNT (AhR nuclear translocator). The heterodimer is a transcription factor, which regulates the transcription of xenobiotic metabolizing enzymes. Expressed in many cells in vertebrates, it is mostly present in neuronal cell types in invertebrates, where it regulates dendritic morphology or feeding behavior. Surprisingly, few investigations have been conducted to unravel the function of the AhR in the central or peripheral nervous systems of vertebrates. In this review, we will present how the AhR regulates neural functions in both invertebrates and vertebrates as deduced mainly from the effects of xenobiotics. We will introduce some of the molecular mechanisms triggered by the well-known AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which impact on neuronal proliferation, differentiation, and survival. Finally, we will point out the common features found in mice that are exposed to pollutants, and in AhR knockout mice.
- Published
- 2018
- Full Text
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8. AhR signaling pathways and regulatory functions.
- Author
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Larigot L, Juricek L, Dairou J, and Coumoul X
- Abstract
Animals and humans are exposed each day to a multitude of chemicals in the air, water and food. They have developed a battery of enzymes and transporters that facilitate the biotransformation and elimination of these compounds. Moreover, a majority of these enzymes and transporters are inducible due to the activation of xenobiotic receptors which act as transcription factors for the regulation of their target genes (such as xenobiotic metabolizing enzymes, see below §4 for the AhR). These receptors include several members of the nuclear/steroid receptor family (CAR for Constitutive Androstane Receptor, PXR for Pregnane X Receptor) but also the Aryl hydrocarbon Receptor or AhR, a member of the bHLH-PAS family (basic Helix-Loop-Helix - Period/ARNT/Single minded). In addition to the regulation of xenobiotic metabolism, numerous alternative functions have been characterized for the AhR since its discovery. These alternative functions will be described in this review along with its endogenous functions as revealed by experiments performed on knock-out animals.
- Published
- 2018
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9. Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis.
- Author
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Shackleford G, Sampathkumar NK, Hichor M, Weill L, Meffre D, Juricek L, Laurendeau I, Chevallier A, Ortonne N, Larousserie F, Herbin M, Bièche I, Coumoul X, Beraneck M, Baulieu EE, Charbonnier F, Pasmant E, and Massaad C
- Subjects
- Animals, Apoptosis, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Cells, Cultured, Humans, Male, Mice, Mice, Inbred C57BL, Myelin Sheath metabolism, Nerve Sheath Neoplasms genetics, Nerve Sheath Neoplasms metabolism, Signal Transduction, Basic Helix-Loop-Helix Transcription Factors physiology, Cell Transformation, Neoplastic pathology, Gene Expression Regulation, Neoplastic, Myelin Sheath pathology, Nerve Sheath Neoplasms pathology, Receptors, Aryl Hydrocarbon physiology
- Abstract
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 ( NF1 ) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples. We report that AHR and the biosynthetic enzymes of its endogenous ligand are overexpressed in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and trimethoxyflavone, induces apoptosis in human MPNST cells. Since AHR dysregulation is observed in these tumors, we investigate AHR involvement in Schwann cell physiology. Hence, we studied the role of AHR in myelin structure and myelin gene regulation in Ahr
-/- mice during myelin development. AHR ablation leads to locomotion defects and provokes thinner myelin sheaths around the axons. We observe a dysregulation of myelin gene expression and myelin developmental markers in Ahr-/- mice. Interestingly, AHR does not directly bind to myelin gene promoters. The inhibition of AHR in vitro and in vivo increased β-catenin levels and stimulated the binding of β-catenin on myelin gene promoters. Taken together, our findings reveal an endogenous role of AHR in peripheral myelination and in peripheral nerve sheath tumors. Finally, we suggest a potential therapeutic approach by targeting AHR in nerve tumors., Competing Interests: The authors declare no conflict of interest.- Published
- 2018
- Full Text
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10. AhR-deficiency as a cause of demyelinating disease and inflammation.
- Author
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Juricek L, Carcaud J, Pelhaitre A, Riday TT, Chevallier A, Lanzini J, Auzeil N, Laprévote O, Dumont F, Jacques S, Letourneur F, Massaad C, Agulhon C, Barouki R, Beraneck M, and Coumoul X
- Subjects
- Animals, Astrocytes metabolism, Cytokines metabolism, Demyelinating Diseases metabolism, Demyelinating Diseases pathology, Disease Models, Animal, Evoked Potentials, Visual, Genetic Association Studies, Inflammation metabolism, Inflammation pathology, Inflammation Mediators metabolism, Mice, Mice, Knockout, Myelin Sheath genetics, Myelin Sheath metabolism, Optic Nerve metabolism, Optic Nerve pathology, Optic Nerve physiopathology, Phenotype, Signal Transduction, Demyelinating Diseases genetics, Genetic Predisposition to Disease, Inflammation genetics, Receptors, Aryl Hydrocarbon deficiency
- Abstract
The Aryl hydrocarbon Receptor(AhR) is among the most important receptors which bind pollutants; however it also regulates signaling pathways independently of such exposure. We previously demonstrated that AhR is expressed during development of the central nervous system(CNS) and that its deletion leads to the occurrence of a congenital nystagmus. Objectives of the present study are to decipher the origin of these deficits, and to identify the role of the AhR in the development of the CNS. We show that the AhR-knockout phenotype develops during early infancy together with deficits in visual-information-processing which are associated with an altered optic nerve myelin sheath, which exhibits modifications in its lipid composition and in the expression of myelin-associated-glycoprotein(MAG), a cell adhesion molecule involved in myelin-maintenance and glia-axon interaction. In addition, we show that the expression of pro-inflammatory cytokines is increased in the impaired optic nerve and confirm that inflammation is causally related with an AhR-dependent decreased expression of MAG. Overall, our findings demonstrate the role of the AhR as a physiological regulator of myelination and inflammatory processes in the developing CNS. It identifies a mechanism by which environmental pollutants might influence CNS myelination and suggest AhR as a relevant drug target for demyelinating diseases.
- Published
- 2017
- Full Text
- View/download PDF
11. Activation of the aryl hydrocarbon receptor by carcinogenic aromatic amines and modulatory effects of their N-acetylated metabolites.
- Author
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Juricek L, Bui LC, Busi F, Pierre S, Guyot E, Lamouri A, Dupret JM, Barouki R, Coumoul X, and Rodrigues-Lima F
- Subjects
- 2-Naphthylamine administration & dosage, 2-Naphthylamine metabolism, 2-Naphthylamine toxicity, Acetylation, Aminobiphenyl Compounds administration & dosage, Aminobiphenyl Compounds metabolism, Aminobiphenyl Compounds toxicity, Benzo(a)pyrene administration & dosage, Benzo(a)pyrene pharmacology, Carcinogens metabolism, Cell Line, Cytochrome P-450 CYP1A1 metabolism, Fluorenes administration & dosage, Fluorenes metabolism, Fluorenes toxicity, Hep G2 Cells, Humans, Liver drug effects, Liver metabolism, Lung drug effects, Lung metabolism, Receptors, Aryl Hydrocarbon metabolism, Carcinogens toxicity, Cytochrome P-450 CYP1A1 genetics, Gene Expression Regulation, Enzymologic drug effects, Receptors, Aryl Hydrocarbon drug effects
- Abstract
Aromatic 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.
- Published
- 2015
- Full Text
- View/download PDF
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