Disruption of Nuclear Receptor Signaling Alters Triphenyl Phosphate-Induced Cardiotoxicity in Zebrafish Embryos
ABSTRACT Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on (1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and (2) high-content screening to identify nuclear receptor ligands thatRead More
Systems toxicology identifies mechanistic impacts of 2-amino-4,6-dinitrotoluene (2A-DNT) exposure in Northern Bobwhite
ABSTRACT Background: A systems toxicology investigation comparing and integrating transcriptomic and proteomic results was conducted to develop holistic effects characterizations for the wildlife bird model, Northern bobwhite (Colinus virginianus) dosed with the explosives degradation product 2-amino-4,6-dinitrotoluene (2A-DNT). A subchronic 60d toxicology bioassay was leveraged where both sexes were dosed via daily gavage with 0, 3, 14, or 30 mg/kg-dRead More
β-apo-13-Carotenone Regulates Retinoid X Receptor Transcriptional Activity Through Tetramerization of the Receptor
ABSTRACT Retinoid X receptor (RXRα) is activated by 9-cis-retinoic acid (9cRA) and regulates transcription as a homodimer or as a heterodimer with other nuclear receptors. We have previously demonstrated that β-apo-13-carotenone, an eccentric cleavage product of β-carotene, antagonizes the activation of RXRα by 9cRA in mammalian cells overexpressing this receptor. However, the molecular mechanism ofRead More
Examination of Retinoid-like Compounds for Human RXRs, RARs, and RORs
View Full Size Research conducted by: Prajakta Albrecht (1), Koji Toyokawa (1), Ewa Maddox (1), Palmer Cramer (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,Read More
Examination of Specificity of Retinoid-like Compounds for Human RXRs, RARs, and RORs
ABSTRACT Vitamin A (retinol) and its metabolites play many physiological roles including cell differentiation, cell proliferation, energy homeostasis, circadian rhythm and immune response. Vitamin A and its metabolites are known to act through retinoid acid receptors (RARs), retinoid-related orphan receptors (RORs) and retinoid x receptors (RXRs). These receptors are also important drug targets, although theRead More
Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil
ABSTRACT Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared with other 3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoylRead More
Differential Activation of Nuclear Receptors by Perflunoriated Fatty Acid Analogs and Natural Fatty Acids: A Comparison of Human, Mouse, and Rat Peroxisome Proliferator-Activated Receptor Receptor-a, -b, and -c, Liver X Receptor-b, and Retinoid X Receptor-a
ABSTRACT Administration of ammonium salts of perfluorooctanoate (PFOA) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (NR) peroxisome proliferator-activated receptor-a (PPARa). Due to its fatty acid structure, PFOA may activate other NRs, such as PPARb, PPARg, liver X receptor (LXR), or retinoid X receptor (RXR). In this study, theRead More