Defying death: the hepatocyte's survival kit

MH Schoemaker*, H Moshage

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

30 Citations (Scopus)

Abstract

Acute liver injury can develop as a consequence of viral hepatitis, drug- or toxin-induced toxicity or rejection after liver transplantation, whereas chronic liver injury can be due to long-term exposure to alcohol, chemicals, chronic viral hepatitis, metabolic or cholestatic disorders. During liver injury, liver cells are exposed to increased levels of cytokines, bile acids and oxidative stress. This results in death of hepatocytes. In contrast, stellate cells become active and are resistant against cell death. Eventually, acute and chronic liver injury is followed by loss of liver function for which no effective therapies are available. Hepatocytes are well equipped with protective mechanisms to prevent cell death. As long as these protective mechanisms can be activated, the balance will be in favour of cell survival. However, the balance between cell survival and cell death is delicate and can be easily tipped towards cell death during liver injury. Therefore understanding the cellular mechanisms controlling death of liver cells is of clinical and scientific importance and can lead to the identification of novel intervention targets. This review describes some of the mechanisms that determine the balance between cell death and cell survival during liver diseases. The strict regulation of apoptotic cell death allows therapeutic intervention strategies. In this light, receptor-mediated apoptosis and mitochondria-mediated cell death are discussed and strategies are provided to selectively interfere with these processes.

Original languageEnglish
Pages (from-to)13-25
Number of pages13
JournalClinical Science
Volume107
Issue number1
Publication statusPublished - Jul-2004

Keywords

  • apoptosis
  • cell death
  • hepatocyte
  • liver injury
  • survival
  • stellate cell
  • therapeutic intervention
  • TUMOR-NECROSIS-FACTOR
  • NF-KAPPA-B
  • MITOCHONDRIAL PERMEABILITY TRANSITION
  • CYTOCHROME-C RELEASE
  • HUMAN HEPATOCELLULAR-CARCINOMA
  • NITRIC-OXIDE SYNTHASE
  • CHOLESTATIC LIVER-INJURY
  • ACTIVATED PROTEIN-KINASE
  • EPIDERMAL-GROWTH-FACTOR
  • HEPATIC STELLATE CELLS

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