Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity
| Autor: | Larry W. Robertson, Gopi S. Gadupudi, Aloysius J. Klingelhutz |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty Glycogenolysis 010501 environmental sciences Biology Toxicology CREB 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Phosphorylation Cyclic AMP Response Element-Binding Protein Beta oxidation 0105 earth and related environmental sciences Fatty acid metabolism Dose-Response Relationship Drug Gluconeogenesis Lipid metabolism General Medicine Polychlorinated Biphenyls Rats 030104 developmental biology Endocrinology chemistry Liver Toxicity biology.protein |
| Zdroj: | Chemical research in toxicology. 29(9) |
| ISSN: | 1520-5010 |
| Popis: | The dioxin-like PCB126 elicits toxicity in various target organs. In rat liver, an alteration in the transcript levels of several genes involved in glucose and fatty acid metabolism provides insights into the origin of its hepatotoxicity. To explore the mechanisms, male Sprague–Dawley rats, fed an AIN-93G diet, were injected with PCB126 (1 or 5 μmol/kg) or corn oil and euthanized after 2 weeks. PCB126 significantly decreased serum glucose levels and the transcript levels of genes of many gluconeogenic and glycogenolytic enzymes under the transcriptional control of a nuclear transcription factor, cAMP response element-binding protein (CREB). As a novel finding, we show that PCB126 significantly decreases CREB phosphorylation, which is important for regulating both gluconeogenesis and fatty acid oxidation in the liver and explains CREB’s integrative effects on both carbohydrate and lipid metabolism in PCB126 toxicity. |
| Databáze: | OpenAIRE |
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