Activation of metallothionein transcription by 4-hydroxynonenal

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...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2010-09, Vol.24 (5), p.330-334
Main Authors: Braithwaite, Elena K., Mattie, Michael D., Freedman, Jonathan H.
Format: Article
Language:English
Subjects:
4-Hydroxynonenal
Aldehydes - metabolism
Aldehydes - pharmacology
Animals
Antioxidants - pharmacology
Cell Line
Chlorocebus aethiops
COS Cells
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression Regulation
Hepatocytes - cytology
Hepatocytes - metabolism
Lipid Peroxides - metabolism
Liver - metabolism
Metallothionein
Metallothionein - biosynthesis
Metallothionein - genetics
Metallothionein - metabolism
Metals - metabolism
Mice
Models, Biological
Oxidation-Reduction
Oxidative Stress
Reactive Oxygen Species
Reactive Oxygen Species - metabolism
Response Elements - genetics
RNA, Messenger - metabolism
Signal Transduction - physiology
Transcription
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcription Factor MTF-1
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation - genetics
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Summary: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. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:330–334, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20342
ISSN:1095-6670
1099-0461
1099-0461
DOI:10.1002/jbt.20342