Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation

X. U. Yang, Cynthia Bradham, David A. Brenner, Mark J. Czaja

Research output: Contribution to journalArticle

Abstract

To deter-mine whether intracellular signaling events involved in apoptosis may also mediate necrosis, the role of the transcription factor AP-1 was investigated in a hepatoma cell model of cellular necrosis induced by oxidant stress. Treatment of the human hepatoma cell line HuH-7 with H2O2 caused dose-dependent necrosis as determined by light microscopy, fluorescent staining, and an absence of DNA fragmentation. H2O2 treatment led to increases in c-fos and c-jun mRNA levels, Jun nuclear kinase activity, and AP-1 DNA binding. AP-1 transcriptional activity measured with an AP-1-driven luciferase reporter gene was also increased. To determine whether this AP-1 activation contributed to H2O2-induced cell necrosis, HuH-7 cells were stably transfected with an antisense c-jun expression vector. Cells expressing antisense c-jun had decreased levels of AP-1 activation and significantly increased survival after H2O2 exposure. These data indicate that AP-1 activation occurs during oxidant-induced cell necrosis and contributes to cell death. Necrosis is therefore not always a passive process but may involve the activation of intracellular signaling pathways similar to those that mediate apoptosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume273
Issue number4 PART 1
StatePublished - 1997

Fingerprint

Transcription Factor AP-1
Hydrogen Peroxide
Necrosis
Liver
Oxidants
Hepatocellular Carcinoma
Apoptosis
DNA Fragmentation
Luciferases
Reporter Genes
Microscopy
Cell Death
Phosphotransferases
Staining and Labeling
Light
Cell Line
Messenger RNA
Survival
DNA

Keywords

  • Apoptosis
  • C-fos
  • C-jun
  • Hepatoma cell

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Yang, X. U., Bradham, C., Brenner, D. A., & Czaja, M. J. (1997). Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation. American Journal of Physiology, 273(4 PART 1).

Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation. / Yang, X. U.; Bradham, Cynthia; Brenner, David A.; Czaja, Mark J.

In: American Journal of Physiology, Vol. 273, No. 4 PART 1, 1997.

Research output: Contribution to journalArticle

Yang, XU, Bradham, C, Brenner, DA & Czaja, MJ 1997, 'Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation', American Journal of Physiology, vol. 273, no. 4 PART 1.
Yang, X. U. ; Bradham, Cynthia ; Brenner, David A. ; Czaja, Mark J. / Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation. In: American Journal of Physiology. 1997 ; Vol. 273, No. 4 PART 1.
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