Dissection of the multiple mechanisms of TNF-α-induced apoptosis in liver injury

Wen Xing Ding, Xiao-Ming Yin

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α-induced hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure. TNF-α exerts a variety of effects that are mediated mainly by TNF-receptor 1 (TNF-R1) in cell death. The activation of TNF-R1 leads to the activation of multiple apoptotic pathways involving the activation of the pro-death Bcl-2 family proteins, reactive oxygen species, C-Jun NH2-terminal kinase, cathepsin B, acidic sphingomyelinase and neutral sphingomyelinase. These pathways are closely interlinked and mainly act on mitochondria, which release the apoptogenic factors and other events, resulting in apoptosis. This article reviews the recent progress in the molecular mechanisms of TNF-α-induced apoptosis in hepatocytes, and discusses how these molecular findings are shaping our understanding of the pathogenesis of liver diseases and our strategy to develop novel therapeutics.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume8
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Dissection
Liver
Tumor Necrosis Factor-alpha
Apoptosis
Sphingomyelin Phosphodiesterase
Chemical activation
Wounds and Injuries
Liver Diseases
Hepatocytes
Alcoholic Hepatitis
Cathepsin B
Mitochondria
Acute Liver Failure
JNK Mitogen-Activated Protein Kinases
Tumor Necrosis Factor Receptors
Cell death
Reperfusion Injury
Hepatitis
Reactive Oxygen Species
Cell Death

Keywords

  • Apoptosis
  • Bcl-2 family proteins
  • Liver injury
  • Mitochondria
  • Reactive oxygen species
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Dissection of the multiple mechanisms of TNF-α-induced apoptosis in liver injury. / Ding, Wen Xing; Yin, Xiao-Ming.

In: Journal of Cellular and Molecular Medicine, Vol. 8, No. 4, 10.2004, p. 445-454.

Research output: Contribution to journalArticle

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