Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor
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ABSTRACT:
PROVIDER: PRJNA495640 | ENA |
REPOSITORIES: ENA
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Project description:Wild type zebrafish (AB strain, https://zfin.org/action/genotype/view/ZDB-GENO-960809-7) were set up for mating overnight, in 3:2 ratios, females and males, respectively. Fertilized embryos from wildtype zebrafish AB strain were used for all experiments and kept in Embryo medium (E3, 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2, 0.33 mM MgSO4) in an incubator at 28ºC. At 1dpf, larvae were manually dechorionated under a stereomicroscope. At 2dpf, zebrafish larvae were divided randomly into the different experimental groups, at a density of 12 larvae per well of a 12 well plate (Corning) in 1.5mL of E3. Three biological replicates of 12 larvae per condition were exposed to different conditions for 4 hours at 28 ºC: DMSO; DMSO + CH223191 (5mM); 3-o-C12-L-HSL (50mM); 3-o-C12-L-HSL (50mM) + CH223191 (5 mM ); 1-hydroxyphenazine (1-HP, 5mM); 1-HP (5mM) + CH223191(5mM) and 1-HP (5mM) + 3-o-C12-L-HSL (50mM).To mention, in experiments using the Aryl hydrocarbon Receptor inhibitor CH223191, larvae were pre-exposed to 5uM of the inhibitor for 2h prior to the start of the experiment and the inhibitor was kept during the experiment. After the desired exposure to diverse ligands, larvae were euthanized with Tricaine (MS-222, 300 µg/mL) and placed in Trizol for RNA isolation. The same experimental layout was performed 5 times, and samples were subjected to microarray hybridization and analysis.
2019-10-01 | GSE121101 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15857: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney GSE15858: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Liver Refer to individual Series
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Project description:The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to the toxic effects of TCDD. Experiment Overall Design: XLK-WG cells (ATCC) were grown to ~90% confluence in RPMI-1640 media supplemented with 20% FBS at 29 degrees and 5% CO2. Cells were subsequently exposed to 100 nM TCDD, FICZ, or DMSO vehicle (0.25%) for 3 hr prior to extraction of total RNA. Experiment Overall Design: Study included three complete biological replicates of each treatment.
2009-07-05 | E-GEOD-16670 | biostudies-arrayexpress
Project description:Therapeutic aryl hydrocarbon receptor (AHR) modulating agents (TAMAs) gained attention in dermatology as non-steroidal anti-inflammatory drugs that improve skin barrier properties. By exploiting AHR’s known ligand promiscuity, we generated novel TAMAs by lead optimization of a selective AHR modulator (SAhRM; SGA360). Twenty-two newly synthesized compounds were screened yielding two novel derivatives, SGA360f and SGA388, in which agonist activity led to enhanced keratinocyte terminal differentiation. We questioned whether SGA derivatives can restore the disturbed epidermal differentiation processes that are known for the key AD-associated T helper-2 cytokine, interleukin-4 (IL-4). We performed genome-wide transcriptomic analysis by bulk RNA-sequencing after co-stimulation of human epidermal equivalents with interleukin-4 (IL-4; AD-HEE) and SGA360 (SAhRM activity), SGA360f or SGA388 (coupling of SAhRM to agonist activity), or TCDD (full AHR agonist).
2023-02-01 | GSE212539 | GEO
Project description:Aryl hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl hydrocarbon receptor-mediated signaling, is overexpressed in highly metastatic human KM12SM CRC cells, with high metastatic capacity to liver, and other highly metastatic CRC cells. Meta-analysis and immunohistochemistry were used to assess the relevance of this protein in CRC. Cellular functions and signaling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments. A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly-metastatic) and KM12SM CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signaling activation of AKT, SRC, and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumor growth and liver metastasis. Furthermore, KM12C (poorly-metastatic) cells ectopically expressing AIP became metastatic to liver. Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.
2023-05-10 | PXD031119 | Pride
Project description:The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR not only evolved to sense pollutants from the environment, but also insults of microbial origin. We demonstrate that bacterial pigmented virulence factors, namely the phenazines pyocyanin and 1-hydroxyphenazine from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, are ligands of AhR. AhR activation leads to degradation of these virulence factors and regulated cytokine and chemokine production. The relevance of AhR to host defense is underlined by heightened susceptibility of AhR-deficient mice, both to P. aeruginosa and M. tuberculosis. Our data demonstrate that AhR senses distinct bacterial virulence factors and controls anti-bacterial responses. We provide evidence for a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigmented virulence factors as a new class of pathogen-associated molecular patterns. Microarray experiments were performed as single-color hybridizations. Quality control and quantification of total RNA amount was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies) and a NanoDrop 1000 spectrophotometer (Kisker).
2014-01-01 | E-GEOD-48130 | biostudies-arrayexpress
Project description:We report sequencing of chromatin immunoprecipitated DNA (ChIP-Seq) of Aryl Hydrocarbon Receptor (AHR) targets from decidual stromal cells with kynurenine treatment and normal decidualization media
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Project description:The aryl hydrocarbon receptor repressor (AHRR) is a bHLH-PAS protein closely related to the aryl hydrocarbon receptor (AHR). AHRR is a transcriptional repressor of AHR and hypoxia-inducible factor (HIF) and is regulated by an AHR-dependent mechanism. Zebrafish possess two AHRR paralogs; AHRRa regulates constitutive AHR signaling during development, while AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, very little is known about the endogenous roles of AHRRs in development and physiology. The objective of this study was to elucidate the role of AHRRs during zebrafish development using a loss-of-function approach followed by microarray analysis. Zebrafish embryos were microinjected with morpholino oligonucleotides (MO) against AHRRa or AHRRb to disrupt endogenous signaling during development. At 72 hours post-fertilization (hpf), embryos were sampled for microarray analysis. Agilent microarray analysis revealed altered expression of 279 and 116 genes with knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes were up-regulated and 182 genes were down-regulated. Among the differentially expressed genes were a large number related to photoreceptor development, including cone-specific genes such as short-wave, medium-wave and long-wave sensitive opsins (opn1sw1, opn1sw2, opn1mw1, opn1lw2), phosphodiesterases (pde6H, pde6C), retinol binding protein (rbp4l), phosducin, and arrestin. These results suggest that AHRRa may be involved in photoreceptor development. In addition, AHRRa knockdown also caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes and down-regulation of 85 genes, without enrichment of genes related to any specific biological process. Overall, these results suggest that AHRRs play multiple roles during development. Three different treatment conditions (Control-MO, AHRRa-MO and AHRRb-MO) and two replicates per treatment
2014-01-15 | E-GEOD-52229 | biostudies-arrayexpress
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages. Skin epidermal cells from 2 individual C57BL/6 mice and 2 individual AhR-deficient mice (deletion of exon2, AhRtm1Bra) were grown for 6-8 weeks in selection medium to propagate melanocytes.
2010-09-05 | E-GEOD-19411 | biostudies-arrayexpress