scholarly journals Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver

Hepatology ◽  
2007 ◽  
Vol 46 (1) ◽  
pp. 209-218 ◽  
Author(s):  
Rushang D. Patel ◽  
Brett D. Hollingshead ◽  
Curtis J. Omiecinski ◽  
Gary H. Perdew
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Human Liver ◽  
Constitutive Androstane Receptor ◽  
Receptor Activation ◽  
Aryl Hydrocarbon

scholarly journals Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 372
Author(s):  
Lisa Goedtke ◽  
Heike Sprenger ◽  
Ute Hofmann ◽  
Felix F. Schmidt ◽  
Helen S. Hammer ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Human Liver ◽  
Constitutive Androstane Receptor ◽  
Liver Cells ◽  
Luciferase Reporter ◽  
Human Liver Cells ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.

scholarly journals Aryl Hydrocarbon Receptor Activation Impairs Extracellular Matrix Remodeling during Zebra Fish fin Regeneration

2006 ◽  
Vol 95 (1) ◽  
pp. 215-226 ◽  
Author(s):  
Eric A. Andreasen ◽  
Lijoy K. Mathew ◽  
Christiane V. Löhr ◽  
Rachelle Hasson ◽  
Robert L. Tanguay
Keyword(s):  
Extracellular Matrix ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Zebra Fish ◽  
Fin Regeneration ◽  
Aryl Hydrocarbon

scholarly journals Detection of Aryl Hydrocarbon Receptor Activation by Some Chemicals in Food Using a Reporter Gene Assay

Foods ◽  
2016 ◽  
Vol 5 (1) ◽  
pp. 15 ◽  
Author(s):  
Yoshiaki Amakura ◽  
Tomoaki Tsutsumi ◽  
Morio Yoshimura ◽  
Masafumi Nakamura ◽  
Hiroshi Handa ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Reporter Gene ◽  
Receptor Activation ◽  
Reporter Gene Assay ◽  
Aryl Hydrocarbon ◽  
Gene Assay

scholarly journals Transporter Gene Regulation in Sandwich Cultured Human Hepatocytes Through the Activation of Constitutive Androstane Receptor (CAR) or Aryl Hydrocarbon Receptor (AhR)

2021 ◽  
Vol 11 ◽  
Author(s):  
Congrong Niu ◽  
Bill Smith ◽  
Yurong Lai
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Constitutive Androstane Receptor ◽  
Gene Induction ◽  
Human Hepatocytes ◽  
Drug Transporter ◽  
Transporter Gene ◽  
Aryl Hydrocarbon ◽  
Multiple Donors ◽  
Metabolizing Enzyme ◽  
Nuclear Receptor Ligands

The induction potentials of ligand-activated nuclear receptors on metabolizing enzyme genes are routinely tested for new chemical entities. However, regulations of drug transporter genes by the nuclear receptor ligands are underappreciated, especially in differentiated human hepatocyte cultures. In this study, gene induction by the ligands of constitutive androstane receptor (CAR) and aryl hydrocarbon receptor (AhR) was characterized in sandwich-cultured human hepatocytes (SCHH) from multiple donors. The cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole (OP), 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO) and phenobarbital (PB) for three days. RNA samples were analyzed by qRT-PCR method. As expected, CITCO, the direct activator, and PB, the indirect activator of CAR, induced CYP3A4 (31 and 40-fold), CYP2B6 (24 and 28-fold) and UGT1A1 (2.9 and 4.2-fold), respectively. Conversely, TCDD and OP, the activators of AhR, induced CYP1A1 (38 and 37-fold), and UGT1A1 (4.3 and 5.0-fold), respectively. In addition, OP but not TCDD induced CY3A4 by about 61-fold. Twenty-four hepatic drug transporter genes were characterized, and of those, SLC51B was induced the most by PB and OP by about 3.3 and 6.5 fold, respectively. Marginal inductions (about 2-fold) of SLC47A1 and SLCO4C1 genes by PB, and ABCG2 gene by TCDD were observed. In contrast, SLC10A1 gene was suppressed about 2-fold by TCDD and CITCO. While clinical relevance of SLC51B gene induction or SLC10A1 gene suppression warrants further investigation, the results verified that the assessment of transporter gene inductions are not required for new drug entities, when a drug does not remarkably induce metabolizing enzyme genes by CAR and AhR activation.

Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lucie Larigot ◽  
Louise Benoit ◽  
Meriem Koual ◽  
Céline Tomkiewicz ◽  
Robert Barouki ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Bacterial Infections ◽  
Critical Role ◽  
Time Frame ◽  
Receptor Activation ◽  
Annual Review ◽  
Publication Date ◽  
Pharmacological Characterization ◽  
Cancer Pathways ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a transcriptional factor that regulates multiple functions following its activation by a variety of ligands, including xenobiotics, natural products, microbiome metabolites, and endogenous molecules. Because of this diversity, the AhR constitutes an exposome receptor. One of its main functions is to regulate several lines of defense against chemical insults and bacterial infections. Indeed, in addition to its well-established detoxication function, it has several functions at physiological barriers, and it plays a critical role in immunomodulation. The AhR is also involved in the development of several organs and their homeostatic maintenance. Its activity depends on the type of ligand and on the time frame of the receptor activation, which can be either sustained or transient, leading in some cases to opposite modes of regulations as illustrated in the regulation of different cancer pathways. The development of selective modulators and their pharmacological characterization are important areas of research. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Sign in / Sign up

Export Citation Format

Share Document