NOX3-derived reactive oxygen species promote TNF-alpha-induced reductions in hepatocyte glycogen levels via a JNK pathway

FEBS Lett. 2010 Mar 5;584(5):995-1000. doi: 10.1016/j.febslet.2010.01.044. Epub 2010 Jan 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Fluorescent Antibody Technique
  • Glycogen / metabolism*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Immunohistochemistry
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Membrane Proteins
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Glycogen
  • NADPH Oxidases
  • Nox3 protein, human
  • JNK Mitogen-Activated Protein Kinases