scholarly journals Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons

2008 ◽  
Vol 104 (5) ◽  
pp. 1415-1429 ◽  
Author(s):  
Chun-Hua Lin ◽  
Shu-Hui Juan ◽  
Chen Yu Wang ◽  
Yu-Yo Sun ◽  
Chih-Ming Chou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Aryl Hydrocarbon

scholarly journals Nascent RNA sequencing defines dynamic aryl hydrocarbon receptor signaling responses to wood smoke particles

2021 ◽  
Author(s):  
Arnav Gupta ◽  
Sarah K. Sasse ◽  
Lynn Sanford ◽  
Margaret A. Gruca ◽  
Robin D. Dowell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Epithelial Cells ◽  
Wood Smoke ◽  
Primary Role ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Wildfire Smoke ◽  
Smoke Particles ◽  
Aryl Hydrocarbon

AbstractTranscriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.

scholarly journals Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Philip Hasel ◽  
Owen Dando ◽  
Zoeb Jiwaji ◽  
Paul Baxter ◽  
Alison C. Todd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Synaptic Activity ◽  
Rna Seq ◽  
Metabolic Cooperation ◽  
Closely Related Species ◽  
Lactate Shuttle ◽  
Activity Dependent ◽  
Elevated Lactate

Abstract The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.

Involvement of aryl hydrocarbon receptor nuclear translocator in EGF-induced c-Jun/Sp1-mediated gene expression

2010 ◽  
Vol 67 (20) ◽  
pp. 3523-3533 ◽  
Author(s):  
Wan-Chen Huang ◽  
Shu-Ting Chen ◽  
Wei-Chiao Chang ◽  
Kwang-Yu Chang ◽  
Wen-Chang Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

scholarly journals Yy1 regulates Senp1 contributing to AMPA receptor GluR1 expression following neuronal depolarization

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Tao Wu ◽  
Mary E. Donohoe
Keyword(s):  
Gene Expression ◽  
Ampa Receptor ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Expression Patterns ◽  
Luciferase Assay ◽  
Regulation Mechanism ◽  
Phosphatase Inhibitors ◽  
Ampa Receptor Subunit

Abstract Background Neuronal activity-induced changes in gene expression patterns are important mediators of neuronal plasticity. Many neuronal genes can be activated or inactivated in response to neuronal depolarization. Mechanisms that activate gene transcription are well established, but activity-dependent mechanisms that silence transcription are less understood. It is also not clear what is the significance of inhibiting these genes during neuronal activity. Methods Quantitative Real Time-PCR, western blot and immunofluorescence staining were performed to examine the expression of Senp1 and GluR1 in mouse cortical neurons. The alterations of Yy1 phosphorylation upon neuronal depolarization and the interaction of Yy1 with Brd4 were studied by protein co-immunoprecipitation. The regulators of Yy1 phosphorylation were identified by phosphatase inhibitors. Chromatin immunoprecipitation, in vitro DNA binding assay, luciferase assay and gene knockdown experiments were used to validate the roles of Yy1 and its phosphorylation as well as Brd4 in regulating Senp1 expression. Results We report that neuronal depolarization deactivates the transcription of the SUMO protease Senp1, an important component regulating synaptic transmission, scaling, and plasticity, through Yy1. In un-stimulated neurons, Senp1 transcription is activated by a Yy1-Brd4 transcription factor protein complex assembled on the Senp1 promoter. Upon membrane depolarization, however, Yy1 is dephosphorylated and the Yy1-Brd4 complex is evicted from the Senp1 promoter, reducing Senp1 transcription levels. Both Yy1 and Senp1 promote the expression of AMPA receptor subunit GluR1, a pivotal component in learning and memory. Conclusions These results reveal an axis of Yy1/Brd4-Senp1 which regulates the expression of GluR1 during neuronal depolarization. This implicates a regulation mechanism in silencing gene expression upon neuronal activity.

scholarly journals Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Cheri L. Lamb ◽  
Giovan N. Cholico ◽  
Daniel E. Perkins ◽  
Michael T. Fewkes ◽  
Julia Thom Oxford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Matrix Remodeling ◽  
Mrna Levels ◽  
Gelatinase Activity ◽  
Ecm Remodeling ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.

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