ABSTRACT Oxysterol receptors LXRs (α and β) are recently reported to be one of the novel and potential therapeutic targets in reducing cell proliferation and tumor growth in different system model. Activation of LXRs is correlated with modification of PI3K/Akt pathway. LXRs are also found to play a critical role in maintaining lipid homeostatais byRead More
Differential modulation of FXR activity by chlorophacinone and ivermectin analogs
ABSTRACT Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10 K chemical collection. In the present study, weRead More
Effects of Munitions Compounds on Xenobiotic-Activated Nuclear Receptors and Signaling Pathways
ABSTRACT Exposure to certain munitions compounds is know to alter physiological functions in test organisms, however little is known about their molecular and cellular effects. Several nuclear receptors are regulated by xenobiotic compounds. These nuclear receptors belong to a class of ligand-activated transcription factors that, when heterodimerized with RXRa and bound to their respective DNARead More
Identification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes
ABSTRACT The apolipoprotein E (APOE) gene is the most highly associated susceptibility locus for late onset Alzheimer’s Disease (AD), and augmenting the beneficial physiological functions of apoE is a proposed therapeutic strategy. In a high throughput phenotypic screen for small molecules that enhance apoE secretion from human CCF-STTG1 astrocytoma cells, we show the chrysanthemic esterRead More
Indigo Announces In Vitro Toxicology Platform
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 inRead More
The Flavone Luteolin Inhibits Liver X Receptor Activation
ABSTRACT Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCRRead More
In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the fame retardant mixture FM 550 and its triarylphosphate and brominated components
ABSTRACT Firemaster®550 (FM 550) is a mixture of brominated and triarylphosphate flame retardants used in polyurethane foam-based products. The primary components are also used in numerous other applications and are thus common household and industrial contaminants. Our previous animal studiessuggested that FM 550 exposure may alter metabolism and cause weight gain. Employing human nuclear receptorRead 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