Abstract
TNF-alpha-induced insulin resistance is associated with generation of reactive oxygen species (ROS). This study aims at defining the link between ROS production and hepatic insulin resistance. Treatment with TNF-alpha increased ROS generation through activating NADPH oxidase 3 (NOX3) in HepG2 hepatocytes. Down-regulation of NOX3 using siRNA prevented TNF-alpha-induced decrease of cellular glycogen. In the cells treated with TNF-alpha, there were NOX3-dependent activation of JNK, inhibition of IRS1 and phosphorylation of AKT/PKB and GSK. In conclusion, the effects of TNF-alpha on hepatic insulin resistance appear to be, at least in part, mediated by NOX3-derived ROS through a JNK pathway.
Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Fluorescent Antibody Technique
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Glycogen / metabolism*
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Hepatocytes / drug effects
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Hepatocytes / metabolism*
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Humans
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Immunohistochemistry
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Insulin Resistance / genetics
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Insulin Resistance / physiology
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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NADPH Oxidases / genetics
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NADPH Oxidases / metabolism*
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RNA, Small Interfering
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Reactive Oxygen Species / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Membrane Proteins
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RNA, Small Interfering
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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Glycogen
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NADPH Oxidases
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Nox3 protein, human
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JNK Mitogen-Activated Protein Kinases