Aryl hydrocarbon receptor-dependent and -independent pathways mediate curcumin anti-aging effects
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE195769 | GEO | 2022/02/01
REPOSITORIES: GEO
Similar Datasets
Project description:Aryl hydrocarbon receptor-dependent and -independent pathways mediate curcumin anti-aging effects
| PRJNA802127 | ENA
Project description: Not available
| S-EPMC9024831 | biostudies-literature
Project description:Conventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr–/–) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr–/– mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD. Keywords: treatment-control and mutant-wildtype
2008-11-01 | GSE10082 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, 6 replicates of dioxin treatment for wildtype mice, and 5 replicates of corn oil treatment for wildtype mice.
2009-09-21 | E-GEOD-15858 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, and 6 replicates per treatment for wildtype mice.
2009-09-21 | E-GEOD-15857 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15858 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15857 | GEO
Project description:VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compound’s ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo. Keywords: effect of compound
2008-02-12 | GSE10463 | GEO
Project description:The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr-/-) B cells proliferate less than AhR-sufficient (Ahr+/+) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr-/- B cells are outcompeted by Ahr+/+ cells. Transcriptome comparison of AhR-deficient and sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.
2016-11-16 | GSE86521 | GEO
Project description:Acinetobacter baumannii is a highly pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. Our results suggest that bacterial infection interacts with host tryptophan metabolism and the transcription factor FOS.
2024-08-05 | PXD053768 | Pride