title: Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity.
abstract: 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.
authors: Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa , Iowa City, Iowa 52242, United States.
authors: Gopi S
authors: GS
authors: Gadupudi
authors: Department of Microbiology, University of Iowa , Iowa City, Iowa 52242, United States.
authors: Aloysius J
authors: AJ
authors: Klingelhutz
authors: Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa , Iowa City, Iowa 52242, United States.
authors: Larry W
authors: LW
authors: Robertson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis / Q000502:physiology*; D050261:Glycogenolysis / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats
chemical_list: D001786:Blood Glucose; D017362:Cyclic AMP Response Element-Binding Protein; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl