Activation of metallothionein transcription by 4-hydroxynonenal

J Biochem Mol Toxicol. 2010 Sep-Oct;24(5):330-4. doi: 10.1002/jbt.20342.

Abstract

Metallothioneins (MTs) protect cells from oxidative damage by scavenging reactive oxygen species (ROS). Concurrent with protecting cells from ROS-mediated damage, MT transcription is induced by ROS. ROS activate transcription by affecting several signal transduction pathways, many of which have been implicated in regulating MT transcription. ROS-activated intracellular signaling is mediated by the stable lipid peroxide 4-hydroxynonenal (HNE). After determining the level of sensitivity of Hepa 1-6 cells to HNE, MT-1 mRNA expression was shown to be induced in a concentration and time-dependent manner after HNE exposure. Finally, using MT-based reporters, HNE was found to induce MT transcription via both antioxidant response and metal response elements. Thus, ROS may activate MT transcription by generating HNE that in turn affects signaling pathways that regulate MT transcription via the transcription factors AP-1 and MTF-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aldehydes / metabolism
  • Aldehydes / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Lipid Peroxides / metabolism
  • Liver / metabolism
  • Metallothionein / biosynthesis
  • Metallothionein / genetics*
  • Metallothionein / metabolism
  • Metals / metabolism
  • Mice
  • Models, Biological
  • Oxidation-Reduction
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Response Elements / genetics
  • Signal Transduction / physiology
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor MTF-1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics*

Substances

  • Aldehydes
  • Antioxidants
  • DNA-Binding Proteins
  • Lipid Peroxides
  • Metals
  • RNA, Messenger
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • Transcription Factors
  • Metallothionein
  • 4-hydroxy-2-nonenal