Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity

Gopi S Gadupudi; Aloysius J Klingelhutz; Larry W Robertson

doi:10.1021/acs.chemrestox.6b00172

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Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity

Journal article

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Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity

Gopi S Gadupudi, Aloysius J Klingelhutz and Larry W Robertson

Chemical research in toxicology, Vol.29(9), pp.1504-1509

09/19/2016

DOI: 10.1021/acs.chemrestox.6b00172

PMCID: PMC6298789

PMID: 27509375

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https://doi.org/10.1021/acs.chemrestox.6b00172View

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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.

Rats

Male

Liver - physiopathology

Dose-Response Relationship, Drug

Cyclic AMP Response Element-Binding Protein - genetics

Gluconeogenesis - physiology

Glycogenolysis - physiology

Animals

Liver - drug effects

Polychlorinated Biphenyls - toxicity

Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors

Cyclic AMP Response Element-Binding Protein - metabolism

Phosphorylation - drug effects

Blood Glucose - metabolism

ISRP Project 1 2015-2020

Synthesis Core

Details

Title: Subtitle: Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity
Creators: Gopi S Gadupudi - Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa , Iowa City, Iowa 52242, United States
Aloysius J Klingelhutz - Department of Microbiology, University of Iowa , Iowa City, Iowa 52242, United States
Larry W Robertson - Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa , Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Chemical research in toxicology, Vol.29(9), pp.1504-1509
DOI: 10.1021/acs.chemrestox.6b00172
PMID: 27509375
PMCID: PMC6298789
NLM abbreviation: Chem Res Toxicol
ISSN: 0893-228X
eISSN: 1520-5010
Publisher: United States
Grant note: P42 ES013661 / NIEHS NIH HHS P30 CA030199 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 09/19/2016
Academic Unit: Microbiology and Immunology; Occupational and Environmental Health; Radiation Oncology; Iowa Superfund Research Program
Record Identifier: 9984001208302771

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