Regulation of hepatocyte apoptosis by oxidative stress

Rajat Singh, Mark J. Czaja

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Oxidative stress has been implicated as the mechanism of hepatocyte injury from numerous agents. Although reactive oxygen species injure cells by the modification of critical cellular macromolecules, recent studies have demonstrated the mechanistic involvement of oxidant stress-induced alterations in signal transduction cascades. Studies in menadione-treated hepatocytes have demonstrated differential effects of mitogen-activated protein kinase activation on hepatocyte death from acute oxidative stress. Activation of the extracellular signal-regulated kinase pathway 1/2 (ERK1/2) confers hepatocyte resistance to death whereas sustained c-Jun N-terminal kinase (JNK)/c-Jun/AP-1 activation promotes apoptosis. Redundant protective signals such as the protein kinase C/protein kinase D pathways also downregulate the JNK/c-Jun/AP-1 cascade and provide resistance to cell death. Although ERK1/2 overactivation also acts as a protective response to chronic oxidative stress, enhanced activation of this kinase sensitizes hepatocytes to death from free fatty acids in this setting. The outcome from challenge with an oxidative stress, therefore, depends on the integration of a series of signaling cascades that both protect against and promote hepatocyte apoptosis.

Original languageEnglish (US)
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue numberSUPPL. 1
DOIs
StatePublished - 2007

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Hepatocytes
Oxidative Stress
Apoptosis
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Vitamin K 3
Mitogen-Activated Protein Kinases
Nonesterified Fatty Acids
Oxidants
Reactive Oxygen Species
Signal Transduction
Cell Death
Phosphotransferases
Down-Regulation
Wounds and Injuries

Keywords

  • Apoptosis
  • c-Jun N-terminal kinase
  • Extracellular signal-regulated kinase 1/2
  • Oxidative stress
  • Protein kinase C

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Regulation of hepatocyte apoptosis by oxidative stress. / Singh, Rajat; Czaja, Mark J.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 22, No. SUPPL. 1, 2007.

Research output: Contribution to journalArticle

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