Rat Aryl Hydrocarbon Receptor (rAhR)
|Product Family||Product Number||Product Description||Technical Manual|
|R06001-32||Rat AhR Reporter Assay System, 3 x 32 assays in 96-well format||Technical Manual|
|R06001||Rat AhR Reporter Assay System, 1 x 96-well format assays||Technical Manual|
Kits are offered in different assay formats to accommodate researchers' needs: 3x 32 and 1x 96 assay formats for screening small numbers of test compounds, as well as custom bulk reagents for HTS applications. Assay systems are all inclusive, providing reporter cells, optimized growth media, media for diluting test compounds, a positive-control agonist, luciferase detection reagent, a white assay plate, a detailed protocol, and a protocol quick guide. All kits are shipped on dry ice.
Rat AhR Reporter Cells are prepared using INDIGO’s proprietary CryoMite™ process. This cryo-preservation method yields exceptional cell viability post-thaw, and provides the convenience of immediately dispensing healthy, division-competent reporter cells into assay plates. There is no need for cumbersome intermediate treatment steps such as spin-and-rinse of cells, viability determinations, cell titer adjustments, or the pre-incubation of reporter cells prior to assay setup.
INDIGO’s Rat Aryl Hydrocarbon Receptor (rAhR) assay kit is an all-inclusive system. In addition to rAhR Reporter Cells, this kit provides two optimized media for use during cell culture and in diluting the user’s test samples, a reference agonist (MeBIO), Luciferase Detection Reagent, and a cell culture-ready assay plate.Assay Kit & Platforms
Bulk assay reagents can be custom manufactured to accommodate any scale of HTS. Please inquire.
INDIGO’s Rat Aryl Hydrocarbon Receptor (AhR) Assay is a cell-based genetic reporter assay that utilizes the luciferase reporter gene Aryl Hdrocarbon Receptor Agonist and Antagonist Assays functionally linked to an AhR-responsive promoter. Thus, quantifying changes in luciferase expression in the treated reporter cells provides a sensitive surrogate measure of the changes in AhR activity. The principle application of this reporter assay system is in the screening of test samples to quantify any functional activity, either agonist or antagonist, that they may exert against rat AhR.
Although technically not a member of the Nuclear Receptor (NR) superfamily, the AhR shares many of the same attributes. The AhR is a member of the basic helix-loop-helix, Per-Arnt-Sim (bHLH-PAS) family of transcription factors and is responsible for the toxicologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, often referred to as simply “dioxin”) and several other related polycyclic aromatic hydrocarbons. The basic mechanism of action of dioxin and related compounds has been extensively studied, in particular as it relates to regulation of cytochrome P450 1A1 (CYP1A1).
AhR is present in most cell types and in the unactivated state is cytosolic and exists in a complex with chaperone proteins such as heat shock protein 90 (Hsp90). Binding of TCDD and related molecules to AhR leads to nuclear translocation and heterodimerization with its partner protein ARNT, another bHLH-PAS family member. The AhR-ARNT heterodimer binds to specific cognate DNA sequence elements known as dioxin/xenobiotic response elements (DRE/XRE) present in the regulatory region of specific genes such as CYP1A1. Binding of the AhR:ARNT heterodimer to these elements, and subsequent recruitment of transcription coactivator complexes, leads to increased transcription of the specific gene, known as “target genes.” There is a battery of genes affected in this manner and targets include certain xenobiotic-metabolizing enzymes, such as CYP1A1,CYP1A2, CYP2B1, and UGT1A6. In addition, genes affected directly and indirectly by the TCDD/AhR-complex code for both inhibitory and stimulatory growth factors and their gene products affect cellular growth and differentiation leading to tumor promotion and carcinogenicity as well as other forms of toxicity.
For more information on AhR, visit the Nuclear Receptor Resource.
The primary application of INDIGO’s cell-based nuclear receptor assays are to quantitatively assess the bioactivity of a test compound as an agonist (activator) or antagonist (inhibition of an agonist response) of a given receptor. Service assays include a positive control reference compound and ‘vehicle’ control for every experiment. A formal study report and all data files are provided to the client upon completion of the study. To receive a quote for your proposed study, complete & submit the online “Request a Quote” form, or, contact an INDIGO Customer Service Representative to discuss your desired study parameters.
ABSTRACT Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previously
Quinazolinone derivative BNUA‐3 ameliorated [NDEA+2‐AAF]‐ induced liver carcinogenesis in SD rats by modulating AhR‐CYP1B1‐Nrf2‐Keap1 pathway
ABSTRACT Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of
View Full Size Research conducted by: Shantanu Roychowdhury (1); Casidy M. Ward (1); Kevin J. Kennedy (1); & Yong Zhao (1) (1) Eurofins Discovery, 6 Research Park Drive, St. Charles, MO 63304 Date of Publication: 2019 Presented at: ISSX 2019 in Portland, OR
ABSTRACT The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we
Differential and Overlapping Effects of 20,23(OH)2D3 and 1,25(OH)2D3 on Gene Expression in Human Epidermal Keratinocytes: Identification of AhR as an Alternative Receptor for 20,23(OH)2D3
ABSTRACT A novel pathway of vitamin D activation by CYP11A has previously been elucidated. To define the mechanism of action of its major dihydroxy-products, we tested the divergence and overlap between the gene expression profiles of human epidermal keratinocytes treated with either CYP11A1-derived 20,23(OH)2D3 or classical 1,25(OH)2D3. Both secosteroids have significant chemical similarity with the
ABSTRACT Psoriasis affects 3% of the population worldwide, and there is no known cure. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, and Crohn’s disease. Psoriasis treatments today include steroid and vitamin D3 cream, ultraviolet light, and immune system suppressing medications such as methotrexate. The T cells responsible for psoriasis
Sedaxane—Use of Nuclear Receptor Transactivation Assays, Toxicogenomics, and Toxicokinetics as Part of a Mode of Action Framework for Rodent Liver Tumors
ABSTRACT Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA is
View Full Size Research conducted by: Koji Toyokawa (1), Ewa Maddox (1), Jack Vanden Huevel (1,2), & Bruce Sherf (1) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences Building, Penn State University, University Park, PA 16802, USA Date of Publication: 2017
In vitro toxicology platform provides predictive model of liver toxicity. Aims to reduce the high rates of drug-induced liver damage State College, PA (May 4, 2016) INDIGO Biosciences, the recognized industry leader in nuclear receptor research, has completed development of an in vitro toxicology platform, meeting the demand for predictive liver toxicity models. INDIGO’s in
Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor
ABSTRACT Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic