scholarly journals Integration of multi-omics data from public resources for the functional analysis of biological networks: molecular-genetic pathways involving aryl hydrocarbon receptor

2016 ◽  
Author(s):  
Serena Dotolo ◽  
Angelo Facchiano
Keyword(s):  
Functional Analysis ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Molecular Networks ◽  
Specific Gene ◽  
Specific Interest ◽  
Data Repositories ◽  
Aryl Hydrocarbon ◽  
Physiological Processes ◽  
Public Data

Omics approaches are widely applied to investigate physiological processes and pathological conditions. Many public data repositories make it possible to extract data for their analyses, comparisons and integrations, provided the availability of suitable tools. Our interest is oriented to the integration of data from different experimental approaches and fields of investigation, covering transcriptomics, proteomics, interactomics, variation data, and drug discovery, in order to highlight hiddens information and to mine new knowledge from available experimental data. Therefore, we look at specific gene and protein functions, for which specific interest has been evidenced, and search for a complete view of their relationships in physiological processes. Moreover, focusing on specific pathologies, we extract from public databases the largest amount of experimental results and analyze them with meta-analysis approaches, to find novel insights on molecular aspects, useful for defining diagnostics or therapy. In this work, our attention is focused on integrative-functional analysis of molecular pathways that involve AHR (Aryl hydrocarbon receptor), a cytosolic transcription factor consisting of several protein domains with distinct functions, including hydrocarbon binding as well as DNA-protein and protein-protein interactions. Previous studies from our lab on this protein give us some specific interest and knowledge about its involvement in many pathologies. Therefore, we investigate it from the physiological point of view, as well as for its role in specific pathologies, also in the view of the molecular network that includes other proteins of interest for the pathology. The functional analysis is executed by means of different open-source bioinformatics platforms, including GeneCards, DSYSMAP, and in particular, Cytoscape platform for realizing and visualizing molecular networks at different levels, in order to improve the knowledge of molecular mechanisms. Furthermore, as an example on a specific pathology, we use the BioGPS platform to extrapolate by Gene Atlas the gene expression profile of our biological targets involved in melanoma, and MelGene DB (a database for melanoma genetic studies and for analysis some important melanoma biomarkers). The poster presents the molecular networks and discusses the potential roles of specifc nodes evidenced by the analysis, also in consideration of the role of disease-related mutations.

scholarly journals Integration of multi-omics data from public resources for the functional analysis of biological networks: molecular-genetic pathways involving aryl hydrocarbon receptor

2016 ◽  
Author(s):  
Serena Dotolo ◽  
Angelo Facchiano
Keyword(s):  
Functional Analysis ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Molecular Networks ◽  
Specific Gene ◽  
Specific Interest ◽  
Data Repositories ◽  
Aryl Hydrocarbon ◽  
Physiological Processes ◽  
Public Data

Omics approaches are widely applied to investigate physiological processes and pathological conditions. Many public data repositories make it possible to extract data for their analyses, comparisons and integrations, provided the availability of suitable tools. Our interest is oriented to the integration of data from different experimental approaches and fields of investigation, covering transcriptomics, proteomics, interactomics, variation data, and drug discovery, in order to highlight hiddens information and to mine new knowledge from available experimental data. Therefore, we look at specific gene and protein functions, for which specific interest has been evidenced, and search for a complete view of their relationships in physiological processes. Moreover, focusing on specific pathologies, we extract from public databases the largest amount of experimental results and analyze them with meta-analysis approaches, to find novel insights on molecular aspects, useful for defining diagnostics or therapy. In this work, our attention is focused on integrative-functional analysis of molecular pathways that involve AHR (Aryl hydrocarbon receptor), a cytosolic transcription factor consisting of several protein domains with distinct functions, including hydrocarbon binding as well as DNA-protein and protein-protein interactions. Previous studies from our lab on this protein give us some specific interest and knowledge about its involvement in many pathologies. Therefore, we investigate it from the physiological point of view, as well as for its role in specific pathologies, also in the view of the molecular network that includes other proteins of interest for the pathology. The functional analysis is executed by means of different open-source bioinformatics platforms, including GeneCards, DSYSMAP, and in particular, Cytoscape platform for realizing and visualizing molecular networks at different levels, in order to improve the knowledge of molecular mechanisms. Furthermore, as an example on a specific pathology, we use the BioGPS platform to extrapolate by Gene Atlas the gene expression profile of our biological targets involved in melanoma, and MelGene DB (a database for melanoma genetic studies and for analysis some important melanoma biomarkers). The poster presents the molecular networks and discusses the potential roles of specifc nodes evidenced by the analysis, also in consideration of the role of disease-related mutations.

scholarly journals Environmental Benzopyrene Attenuates Stemness of Placenta-Derived Mesenchymal Stem Cells via Aryl Hydrocarbon Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
June Seok Heo ◽  
Ja-Yun Lim ◽  
Sangshin Pyo ◽  
Dae Wui Yoon ◽  
Dongsook Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Cell Activity ◽  
Bone Diseases ◽  
Purine Derivative ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated. In the present study, we aimed to investigate the effects of BP on placenta-derived mesenchymal stem cells (PD-MSCs) in vitro. We found that the AhR in PD-MSCs was expressed under the treatment of BP, and its activation markedly disrupted osteogenic differentiation through the alteration of stemness activity of PD-MSCs. Moreover, BP treatment significantly reduced the proliferation activity of PD-MSCs and expression of pluripotent markers through the induction of AhR. Treatment with StemRegenin 1 (SR1), a purine derivative that antagonizes the AhR, effectively prevented BP-induced reduction of the proliferation and differentiation activity of PD-MSCs. In this study, we found that BP treatment in PD-MSCs markedly obstructs PD-MSC stemness through AhR signaling. Noteworthy, SR1-mediated MSC application will contribute to new perspectives on MSC-based therapies for air pollution-related bone diseases.

scholarly journals Aryl hydrocarbon receptor signaling pathway plays important roles in the proliferative and metabolic properties of bone marrow mesenchymal stromal cells

2021 ◽  
Author(s):  
Yan Jia ◽  
Youshan Zhao ◽  
Zheng Zhang ◽  
Lei Shi ◽  
Ying Fang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aryl Hydrocarbon Receptor ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway ◽  
Metabolic Properties

Abstract Bone marrow mesenchymal stromal cells (BMMSCs) are widely sourced and easily amplified in vitro; thus, they have a great potential in the treatment of hemopathies. Recent findings suggested that BMMSCs express the aryl hydrocarbon receptor (AHR). However, few studies have reported on the regulation of proliferative behaviors and metabolism by AHR in BMMSCs. In the present study, we found that activating AHR reduced the proliferation of BMMSCs and enhanced their mitochondrial function, whereas inhibiting AHR exerted the opposite effects. This study may provide the basis for further unveiling the molecular mechanisms and therapeutic potential of AHR in BMMSCs.

FUNCTIONAL ANALYSIS OF SIX HUMAN ARYL HYDROCARBON RECEPTOR VARIANTS IN A JAPANESE POPULATION

2005 ◽  
Vol 33 (8) ◽  
pp. 1254-1260 ◽  
Author(s):  
Satoru Koyano ◽  
Yoshiro Saito ◽  
Hiromi Fukushima-Uesaka ◽  
Seiichi Ishida ◽  
Shogo Ozawa ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Aryl Hydrocarbon Receptor ◽  
Japanese Population ◽  
Aryl Hydrocarbon

scholarly journals AIP mutations impair AhR signaling in pituitary adenoma patients fibroblasts and in GH3 cells

2016 ◽  
Vol 23 (5) ◽  
pp. 433-443 ◽  
Author(s):  
Anne-Lise Lecoq ◽  
Say Viengchareun ◽  
Mirella Hage ◽  
Jérôme Bouligand ◽  
Jacques Young ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Protein Level ◽  
Pituitary Adenomas ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Human Fibroblasts ◽  
Gh3 Cells ◽  
Dependent Manner ◽  
Aryl Hydrocarbon ◽  
The Impact

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP. Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner.

Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress

2009 ◽  
Vol 296 (4) ◽  
pp. E721-E730 ◽  
Author(s):  
Tsuyoshi Shimada ◽  
Nobuhiko Hiramatsu ◽  
Kunihiro Hayakawa ◽  
Shuhei Takahashi ◽  
Ayumi Kasai ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Suppressive Effect ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Aryl Hydrocarbon

Cigarette smoking decreases body weight, whereas molecular mechanisms underlying this phenomenon have not been elucidated. In this report, we investigated regulation of adipogenesis by cigarette smoke and involvement of aryl hydrocarbon receptor (AhR) and endoplasmic reticulum (ER) stress. We found that cigarette smoke extract (CSE) inhibited differentiation of preadipocytes into adipocytes dose dependently. It was associated with a decrease in lipid accumulation, blunted expression of adipocyte markers (adiponectin, PPAR-γ, and C/EBPα), and sustained expression of a preadipocyte marker MCP-1. CSE markedly induced activation of AhR, and AhR agonists (2,3,7,8-tetrachlorodibenzo- p-dioxin, benzo[ a]pyrene and 3-methylcholanthrene) reproduced the inhibitory effect of CSE on adipocyte differentiation. Furthermore, knockout of the AhR gene or blockade of AhR by a dominant-negative mutant attenuated the suppressive effects of CSE on adipocyte differentiation. We also found that CSE induced ER stress in preadipocytes, and ER stress inducers (thapsigargin, tunicamycin, and A23187) reproduced the suppressive effect of CSE on the differentiation of preadipocytes. Interestingly, AhR agonists did not cause ER stress, and ER stress inducers did not activate AhR. These results suggested that cigarette smoke has the potential to inhibit adipocyte differentiation via dual, independent mechanisms, i.e., through activation of the AhR pathway and induction of the unfolded protein response.

scholarly journals Influence of the Aryl Hydrocarbon Receptor Activating Environmental Pollutants on Autism Spectrum Disorder

2021 ◽  
Vol 22 (17) ◽  
pp. 9258
Author(s):  
Hevna Dhulkifle ◽  
Abdelali Agouni ◽  
Asad Zeidan ◽  
Mohammed Saif Al-Kuwari ◽  
Aijaz Parray ◽  
...  
Keyword(s):  
Risk Factors ◽  
Autism Spectrum Disorder ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Environmental Pollutants ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Development Communication ◽  
Aryl Hydrocarbon ◽  
The Impact

Autism spectrum disorder (ASD) is an umbrella term that includes many different disorders that affect the development, communication, and behavior of an individual. Prevalence of ASD has risen exponentially in the past couple of decades. ASD has a complex etiology and traditionally recognized risk factors only account for a small percentage of incidence of the disorder. Recent studies have examined factors beyond the conventional risk factors (e.g., environmental pollution). There has been an increase in air pollution since the beginning of industrialization. Most environmental pollutants cause toxicities through activation of several cellular receptors, such as the aryl hydrocarbon receptor (AhR)/cytochrome P450 (CYPs) pathway. There is little research on the involvement of AhR in contributing to ASD. Although a few reviews have discussed and addressed the link between increased prevalence of ASD and exposure to environmental pollutants, the mechanism governing this effect, specifically the role of AhR in ASD development and the molecular mechanisms involved, have not been discussed or reviewed before. This article reviews the state of knowledge regarding the impact of the AhR/CYP pathway modulation upon exposure to environmental pollutants on ASD risk, incidence, and development. It also explores the molecular mechanisms involved, such as epigenesis and polymorphism. In addition, the review explores possible new AhR-mediated mechanisms of several drugs used for treatment of ASD, such as sulforaphane, resveratrol, haloperidol, and metformin.

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