Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions

Oncogene. 1996 May 16;12(10):2045-50.


Inhibition of the respiratory chain reaction by cyanide, rotenone or antimycin A (chemical hypoxia) induces necrotic cell death characterized by apparently intact chromatin, remarkable mitochondrial swelling with loss of crista structure, and loss of plasma membrane integrity. The treatments induce no apoptotic cell death, as defined by fragmented nuclei with condensed chromatin, fragmented or condensed cytoplasm. The anti-apoptotic proteins Bcl-2 and Bcl-xL effectively retard the chemical hypoxia-induced necrotic cell death. The necrotic cell death is also retarded by inhibitors of ICE(-like) proteases, including interleukin-1beta converting enzyme (ICE), which are common mediators of apoptosis. These results indicate that Bcl-2/Bcl-xL and ICE(-like) proteases modulate apoptotic and at least some forms of necrotic cell death. Both cell death pathways appear to involve some common mediators; however necrotic or apoptotic cell death signals might be transduced through multiple pathways, because Bcl-2/ Bcl-xL or inhibitors of ICE(-like) proteases are relatively less potent in blocking necrotic cell death than in preventing apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimycin A / toxicity
  • Apoptosis / drug effects*
  • Apoptosis / physiology*
  • Carcinoma, Hepatocellular / pathology
  • Caspase 1
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cysteine Endopeptidases / drug effects*
  • Cysteine Endopeptidases / physiology
  • DNA, Complementary / genetics
  • Humans
  • Molecular Sequence Data
  • Necrosis / chemically induced
  • Necrosis / physiopathology
  • PC12 Cells
  • Potassium Cyanide / toxicity
  • Protease Inhibitors / pharmacology*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Rotenone / toxicity
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • bcl-X Protein


  • BCL2L1 protein, human
  • Bcl2l1 protein, rat
  • DNA, Complementary
  • Protease Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Rotenone
  • Antimycin A
  • Cysteine Endopeptidases
  • Caspase 1
  • Potassium Cyanide