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Transcriptomic analysis across liver diseases reveals disease-modulating activation of constitutive androstane receptor in cholestasis.
JHEP Rep
October 2020
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Background & Aims: Liver diseases are caused by many factors, such as genetics, nutrition, and viruses. Therefore, it is important to delineate transcriptomic changes that occur in various liver diseases.
Methods: We performed high-throughput sequencing of mouse livers with diverse types of injuries, including cholestasis, diet-induced steatosis, and partial hepatectomy.
Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver.
Biochem Pharmacol
February 2018
Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address:
Pregnane X receptor (PXR) is a nuclear receptor that senses chemical environment and is activated by numerous clinically used drugs and environmental contaminants. Previous studies have indicated that several drugs known to activate PXR appear to induce glucose intolerance. We now aimed to reveal the role of PXR in drug-induced glucose intolerance and characterize the mechanisms involved.
View Article and Find Full Text PDFInduction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.
Mol Pharmacol
September 2016
Department of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.)
Article Synopsis
- * In a study with mice, those treated with phenytoin showed reduced T4, lower levels of important brain proteins, and changes in brain structure, indicating neurodevelopmental issues.
- * Replacing T4 in treated mice helped reduce abnormal brain structure changes, suggesting that low T4 due to UGT1A1 induction is linked to the neurodevelopmental disorders caused by anticonvulsants.
Organic anion transporting polypeptide 2 transports valproic acid in rat brain microvascular endothelial cells.
Neurol Res
July 2016
a Department of Neurology , Children's Hospital of Chongqing Medical University, Chongqing , China.
Objectives: Abnormal drug transporter expression or function in the brain may lead to decreased concentrations of antiepileptic drugs (AEDs) in the central nervous system in patients with drug-resistant epilepsy. We previously showed the influx transporter organic anion transport polypeptide 2 (Oatp2) was expressed in rat brain microvascular endothelial cells (BMECs). Seizures decrease expression of Oatp2, but it remains unclear whether Oatp2 transports AEDs.
View Article and Find Full Text PDFActivation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice.
PLoS One
December 2012
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN) in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues.
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