Nuclear receptors and xenobiotic metabolism. Medical search. Frequent questions

The constitutive androstane receptor (CAR, NR1I3) plays a key role in the transcriptional activation of genes that encode xenobiotic/steroid and drug metabolizing enzymes. (biomedcentral.com)
The constitutive androstane receptor and pregnane X receptor in the brain. (axonmedchem.com)
DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor. (axonmedchem.com)
Scholars@Duke publication: Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor. (duke.edu)
IR0 (inverted repeat with zero intervening bases) motifs located in the 5-flanking regions of rodent SULT2A genes are required for transcriptional activation by PXR and other nuclear receptors, including constitutive androstane receptor, farnesoid X receptor and vitamin D receptor. (eurekaselect.com)
Sex-Differential Responses of Tumor Promotion-Associated Genes and Dysregulation of Novel Long Noncoding RNAs in Constitutive Androstane Receptor-Activated Mouse Liver. (nih.gov)
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. (nih.gov)
The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. (omeka.net)

In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 (nuclear Receptor subfamily 1, group I, member 2) gene. (wikipedia.org)
Human pregnane X receptor (PXR) is a major nuclear receptor that upregulates the expression of drug-metabolizing enzymes such as CYP3A4. (aspetjournals.org)
One such transcription factor is the pregnane X receptor (PXR). (aspetjournals.org)
It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. (dundee.ac.uk)
The pregnane x receptor (PXR, NR1I2) was first identified in 1998 as a member of the NR superfamily. (ku.edu)
To understand how SGD might affect other drugs , researchers from the Central South University in China investigated its effect on the pregnane X receptor (PXR)-mediated transcriptional regulation of cytochrome P450 3A4 (CYP3A4) and the drug transporter multidrug resistance protein 1 (MDR1) in vitro. (chemotherapy.news)
To do this, they investigated the effect of SGD on the pregnane X receptor (PXR)-mediated transcriptional regulation of cytochrome P450 3A4 (CYP3A4) and the drug transporter multi-drug resistance protein 1 (MDR1) in vitro. (chemotherapy.news)
The Interface between Cell Signaling Pathways and Pregnane X Receptor" by Robert S. Rogers, Annemarie Parker et al. (kansascity.edu)
Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. (kansascity.edu)
Pregnane X receptor (PXR) is a nuclear receptor that regulates a number of genes encoding drug metabolism enzymes and transporters and plays a key role in xeno- and endobiotic detoxification. (greenmedinfo.com)
The transcriptional control of rodent and human hepatic SULT2A expression is subject to trans-activation by the environmental sensor, pregnane X receptor (PXR). (eurekaselect.com)
A member of the nuclear receptor superfamily (subfamily 1, group I, member 3 [NR1i3]) involved, along with PREGNANE X RECEPTOR, in regulation of cellular responses to the exogenous and endogenous chemicals such as detoxification of XENOBIOTICS. (bvsalud.org)

NR1I3) is expressed primarily in liver and regulates the expression of genes involved in xenobiotic metabolism as well as hormone, energy, and lipid homeostasis. (aspetjournals.org)
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod. (uib.no)
NR1I3) is a critical xenobiotic sensor that regulates xenobiotic metabolism, drug clearance, energy and lipid homoeostasis, cell proliferation and development. (duke.edu)
In addition, risperidone influences adipocyte metabolism, differentiation, and lipid accumulation-related functions through transcriptome analysis. (frontiersin.org)
Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. (affbiotech.com)
In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. (omeka.net)
Obesogens are considered foreign chemical compounds, or toxins, that disrupt normal development and the balance of lipid metabolism. (connersclinic.com)

Glucocorticoid-inducible rat hepatic SULT1A1 gene transcription occurs through a glucocorticoid receptor (GR)-mediated mechanism, while human hepatic SULT1A1 does not display GRinducible expression. (eurekaselect.com)

PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. (wikipedia.org)
The superfamily of nuclear hormone receptor comprises a group of transcription factors that play significant roles in response to a number of biological regulators. (biomedcentral.com)
sselw Keywords CYP2C human transcriptional regulation, induction medicines, nuclear receptor liver hypoxia Introduction The cytochromes P450 are a superfamily of enzymes that catalyze the metabolism of medicines and chemical compounds, and xenobiotics a large number of Ecological compounds endogenously. (dna-pkinhibitors.com)
Emerging evidence suggests that liver-enriched transcription factors, the aryl hydrocarbon (Ah) receptor and members of the nuclear receptor transcription factor superfamily all play integrated roles in the control of sulfotransferase gene transcription. (eurekaselect.com)

Nuclear Receptors (NRs), that include steroid hormone receptors, are intra-cellular transcription factors that regulate gene expression in response to their cognate ligands. (jnu.ac.in)
The mechanisms by which these toxins disrupt the body's metabolism is multi-layered and includes the dysregulation of sex steroid synthesis, disruption in regulation of appetite and satiety, and a reprogramming of metabolic set points. (connersclinic.com)

This finding provides a novel concept that paraspeckles formed by liquid-liquid phase separation potentially affect drug metabolism via negative regulation of PXR function. (aspetjournals.org)
Regulation of gene transcription is controlled in part by nuclear receptors that function coordinately with coregulator proteins. (aspetjournals.org)
Members of this family of receptors are involved in regulation of numerous physiological and patho-physiological processes and have great potential as targets for the treatment of diseases such as cancer, diabetes, coronary heart disease and asthma. (jnu.ac.in)
Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond. (illumina.com)
Her current research interests and scientific experience include: bioinspired engineering, toxicology and drug metabolism, liver cell biology, mechanisms regulating gene expression and differentiation, regulation of nuclear receptors and transcriptional activation in hepatocytes by xenobiotics, human cell isolation and cryopreservation techniques. (selectbiosciences.com)
The up-regulation of transcription CEP-18770 chemical structure of those genes in response to xenobiotics and stero Of. (dna-pkinhibitors.com)
Unlike the well known up-regulation of CYP1A1, expression of rat hepatic aryl (SULT1A1) and hydroxysteroid (SULT2A) sulfotransferase is suppressed in response to treatment with the prototypic Ah receptor ligand, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. (eurekaselect.com)
Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. (omeka.net)

Miembro de la superfamilia de receptores nucleares (subfamilia 1, grupo I, miembro 3 [NR1i3]) implicado, junto con el RECEPTOR X DE PREGANO, en la regulación de las respuestas celulares a las sustancias químicas exógenas y endógenas como la desintoxicación de XENOBIÓTICOS. (bvsalud.org)

Structure-activity relationships of FXR-active compounds revealed by this screening were then compared against the androgen receptor, estrogen receptor α, peroxisome proliferator-activated receptors δ and γ and the vitamin D receptor. (nature.com)
Agonistic and potentiating effects of perfluoroalkyl substances (PFAS) on the Atlantic cod (Gadus morhua) peroxisome proliferator-activated receptors (Ppars). (uib.no)

The farnesoid X receptor (FXR) regulates the homeostasis of bile acids, lipids and glucose. (nature.com)

Despite the growing interest in FXR ligands in drug discovery, little is known with regard to the roles of FXR in mediating or protecting xenobiotic-induced toxicity. (nature.com)

PXR is mainly associated with cellular response to xenobiotics, which includes the induction of enzymes involved in drug oxidation and conjugation. (chemotherapy.news)

At NCI, I worked on the cloning and characterization of liver carboxylesterases and was involved in the early studies leading to the development of a knockout mouse for the nuclear receptor PPARα. (ucsf.edu)
The role of the PPAR nuclear receptors in regulating the vascular effects of these eicosanoids is also being studied. (ucsf.edu)
Peroxisome proliferator activated receptor α (PPARα) mediates the induction of human, but not rat, hepatic SULT2A gene transcription, thus implicating a role for fatty acids as endogenous regulators of hepatic sulfonation in humans. (eurekaselect.com)
It is also related to increased adiponectin (APN) expression associated with adipocyte differentiation, as well as the expression of adipogenic genes such as peroxisome proliferator-activated receptor ( PPAR) ( 22 , 23 ). (frontiersin.org)

Liver-enriched nuclear receptor (NR) proteins regulate the expression and activity of several pivotal hepatic biochemical pathways including the uptake, metabolism and excretion of cholesterol, bile acids, glucose, and xenobiotic compounds from the body. (ku.edu)
Because endogenous chemicals bind and activate FXR, it is important to examine which xenobiotic compounds would disrupt normal receptor function. (nature.com)
Pgp is expressed in epithelial tissues throughout the body and recognizes a large number of compounds and xenobiotics . (chemotherapy.news)
Substituted Two- To Five-Ring Polycyclic Aromatic Compounds Are Potent Agonists of Atlantic Cod (Gadus morhua) Aryl Hydrocarbon Receptors Ahr1a and Ahr2a. (uib.no)
The metabolism of 2,3,7,8-TCDD and related compounds is required for urinary and biliary excretion, and the rate of metabolism is thought to play a major role in regulating the rate of elimination (and detoxification) of these compounds (Van den Berg et al. (cdc.gov)

The SUMOylation and ubiquitination of the PXR protein functions to feedback-repress the inflammatory and xenobiotic responses, respectively. (ku.edu)

Furthermore, daily fluctuations in hepatic P450 monooxygenase activities responsible for the first phase of metabolism of various xenobiotics are well known. (biomedcentral.com)
CellzDirect successfully translated and commercialized technology from academic research to supply the pharmaceutical industry with hepatic cell products and services for safety assessment and drug-metabolism studies. (selectbiosciences.com)
The transcription factor networks that regulate basal and xenobiotic-modulated expression of the hepatic sulfotransferases affect the dynamics of xenobiotic detoxication, carcinogen bioactivation and metabolic homeostasis. (eurekaselect.com)

My research is in the area of xenobiotic/endobiotic metabolism and transport. (ucsf.edu)

PXR is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. (wikipedia.org)
Intersecting analysis, molecular docking, and pathway validation analysis showed that risperidone influences the adipocytokine signaling pathway by targeting MAPK14 (mitogen-activated protein kinase 14), MAPK8 (mitogen-activated protein kinase 8), and RXRA (retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid β-oxidation by decreasing STAT3 (signal transducer and activator of transcription 3) expression and phosphorylation. (frontiersin.org)

One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is responsible for the metabolism of many drugs. (wikipedia.org)
This induction results in its own metabolism. (dundee.ac.uk)
The utmost induction of transcriptional CYP2C genes seems to become reached attributable to a cross talk with the coordination concerning drug use nuclear receptors, liver components and co-activators. (dna-pkinhibitors.com)
In the present study, we demonstrate that proteasomal inhibition markedly disrupts CAR function, repressing CAR nuclear trafficking, disrupting CAR's interaction with nuclear co-activators and inhibiting induction of CAR target gene responses in human primary hepatocytes following treatment with either PB or CITCO. (duke.edu)
HT29-Lucia™ AhR cells are engineered from the human HT-29 colon adenocarcinoma cell line for the study of the aryl hydrocarbon receptor (AhR) genomic signaling induction (see details), by monitoring the activity of the Lucia luciferase reporter protein. (invivogen.com)

This article constitutes an in-depth review of the pharmacology, metabolism, toxicology and biosafety aspects of tocotrienols. (biomedcentral.com)
She has led in vitro toxicology and drug metabolism teams in GlaxoSmithKline and AstraZeneca. (selectbiosciences.com)

PXR is a nuclear receptor expressed in the liver and the intestine - two organs involved in the absorption, distribution, metabolism, and elimination of xenobiotics (foreign substances) and endobiotics (present in the host). (chemotherapy.news)
Single PFAS and PFAS mixtures affect nuclear receptor- and oxidative stress-related pathways in precision-cut liver slices of Atlantic cod (Gadus morhua). (uib.no)
Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology. (nih.gov)
Protein-coding genes dysregulated by 3 h TCPOBOP exposure were strongly enriched in KEGG pathways of xenobiotic and drug metabolism, with stronger and more extensive gene responses observed in female than male liver. (nih.gov)

Furthermore, results obtained from mammalian two-hybrid experiments assessing various domain configurations of the respective receptors showed that full-length DAX-1 inhibited the CAR-SRC1 interaction by approximately 50%, whereas the same interaction was restored to 90% of control when the DAX-1 transcription silencing domain was deleted. (aspetjournals.org)
Antioxidant genes such as ferritin are transcriptionally activated in oxidative stress via the antioxidant responsive element (ARE), to which nuclear factor-E2-related factor 2 (Nrf2) binds and activates transcription. (embl.de)
The Nuclear Receptor family is a large group of ligand-activated transcription factors with 48 members presently identified in the human genome. (jnu.ac.in)
This review focuses on the xenobiotic sensors and transcription factor systems that regulate sulfotransferase gene expression. (eurekaselect.com)

Ly6C high MC exhibited activated neutrophil degranulation, lysosome, cytokine production/receptor interaction and myeloid cell activation pathways, and Ly6C low MC presented features of lymphocyte immunity pathways in both mice. (frontiersin.org)
The aryl hydrocarbon receptor (AHR) is regarded as an important homeostatic transcriptional regulator within physiological and pathophysiological processes, including xenobiotic metabolism, endocrine function, immunity, and cancer. (aspetjournals.org)
Aryl hydrocarbon receptor and intestinal immunity. (invivogen.com)
2018. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. (invivogen.com)

A major research effort is on the metabolism of arachidonic acid by the cytochrome P450 and epoxide hydrolase enzymes. (ucsf.edu)
Over the past decade, it has been well established that PXR functions as a master-regulator of xenobiotic- and drug-inducible expression and activity of numerous genes that encode key members of the phase I and phase II metabolic enzymes, as well as several membrane transporter proteins. (ku.edu)

Like other type II nuclear receptors, when activated, it forms a heterodimer with the retinoid X receptor, and binds to hormone response elements on DNA which elicits expression of gene products. (wikipedia.org)

Many nuclear receptors are key metabolic regulators. (csh-asia.org)

INDIGO's Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor Alpha (ERα) bioassay have been approved by the California Water Boards, State Water Resources Control Board, for use as bioanalytical screening tools for Constituents of Emerging Concern (CECs) in recycled water. (indigobiosciences.com)
The aryl hydrocarborn receptor (AhR) is a ligand-dependent transcriptional factor widely expressed in barrier tissues [1]. (invivogen.com)

After network pharmacology and GO analysis, risperidone was found to influence cellular metabolism. (frontiersin.org)

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. (affbiotech.com)

In this report, DAX-1, a nuclear receptor family member with corepressor properties, was identified as a potent CAR regulator. (aspetjournals.org)
Studies on post-translational modification of PXR indicate how this protein is converted from a positive regulator in drug metabolism into a transcriptional repressor in inflammatory response. (ku.edu)

These results suggest that paraspeckles play a role in trapping nuclear PXR in the absence of the ligand to negatively regulate transactivation of its downstream gene. (aspetjournals.org)
Risperidone-induced weight gain is associated with a number of factors, including gene polymorphisms ( 12 - 14 ), exercise ( 15 - 17 ), peripheral molecules ( 18 ), and hyperphagia caused by regulating the expression of melanocortin-4 receptor (MC4R), neuropeptide Y (NPY), and agouti-related peptide (AgRP) ( 19 - 21 ). (frontiersin.org)

Ly6C high MC presented downregulated co-stimulatory receptors (CD2, GITR, and TIM1) which direct immune cell proliferation, and upregulated co-stimulatory ligands (LIGHT and SEMA4A) which trigger antigen priming and differentiation. (frontiersin.org)
Besides xenobiotics, including the prototypic AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a variety of dietary-derived AhR ligands have been identified, many of which are byproducts of tryptophan (Trp) metabolism [2]. (invivogen.com)

Unlike other SGAs, such as clozapine and olanzapine, risperidone is a derivative of benzisoxazole with multiple receptor antagonist properties, making it more effective against negative symptoms and more beneficial on both affective symptoms and cognitive impairments ( 11 ). (frontiersin.org)

AhR heterodimerizes with AhR nuclear translocator (ARNT) before binding to dioxin response elements (DREs) in the upstream regulatory regions of AhR target genes, such as the cytochrome P450-dependent monooxygenase Cyp1a1, the AhR repressor (AhRR), and the IL-22 interleukin. (invivogen.com)

While such functions for glucocorticoids and thyroid hormone have been known for decades, those of the receptors for fatty acids, bile acids, and xenobiotics, for example, are still emerging. (csh-asia.org)

Xenobiotic metabolism and its physiological consequences in high-Antarctic Notothenioid fishes. (uib.no)

PXR is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the detoxification and clearance of these substances from the body. (wikipedia.org)
CAR plays an important role orchestrating the metabolism and detoxification of potentially toxic chemicals, by upregulating genes that are involved in the clearance of both xenobiotics and endobiotics. (axonmedchem.com)

Lower plasma alpha-carboxyethyl-hydroxychroman after deuterium-labeled alpha-tocopherol supplementation suggests decreased vitamin E metabolism in smokers. (oregonstate.edu)
Vitamin E, nuclear receptors and xenobiotic metabolism. (oregonstate.edu)
Polycyclic aromatic hydrocarbons modulate the activity of Atlantic cod (Gadus morhua) vitamin D receptor paralogs in vitro. (uib.no)

Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. (omeka.net)

The Axelrod Award was established in 1991 to honor the memory of the eminent American pharmacologist who shaped the fields of neuroscience, drug metabolism, and biochemistry and who served as a mentor for numerous eminent pharmacologists around the world. (aspet.org)
Dr. Croyle has been selected to receive research funding to investigate novel regulatory mechanisms of drug metabolism in the context of active infection with SARS-CoV-2 and after recovery. (aspet.org)
Drug Metabolism and Disposition , 38 (7), 1046-1053. (dundee.ac.uk)
Taken together, the work presented in this dissertation contributes to understanding the interface between PXR, drug metabolism, and inflammation, which is expected to produce new opportunities for the development of novel therapeutic strategies. (ku.edu)
The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. (kansascity.edu)

Grün and Blumber's study titled, " Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling ," confirmed that the calories-in-calories-out model might not be the full story. (connersclinic.com)

Anatomy19

Organisms9

Diseases2

Chemicals and Drugs134

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes64

Information Science4

Health Care1

Constitutive androsta8

Pregnane12

Lipid7

GLUCOCORTICOID-RECEPTOR1

Superfamily4

Steroid2

Regulation8

NR1I31

Peroxisome prolifera2

Farnesoid1

Protecting xenobiotic-induced1

Response to xenobiotics1

PPAR4

Compounds5

Ubiquitination1

Hepatic3

Endobiotic metabolism1

Retinoic2

Induction5

Toxicology2

Liver4

Transcription4

Immunity4

Enzymes2

Forms a heterodimer1

Metabolic1

Aryl2

Pharmacology1

Binds1

Regulator2

Gene2

Ligands2

Antagonist1

Cytochrome1

Hormone1

Physiological1

Detoxification2

Vitamin3

Lipids1

Drug5

Endocrine1