An interleukin-1 Beta-Converting Enzyme-Like Protease Is a Common Mediator of Apoptosis in Thymocytes

FEBS Lett. 1995 Nov 20;375(3):283-8. doi: 10.1016/0014-5793(95)01228-7.

Abstract

Apoptosis was induced in thymocytes using diverse stimuli in order to identify events within a common apoptotic pathway. Benzyloxycarbonyl-valinyl-alaninyl-aspartyl fluoromethyl ketone (Z-VAD.FMK), an interleukin-1 beta-converting enzyme (ICE)-like protease inhibitor, inhibited apoptosis assessed by flow cytometry, proteolysis of poly (ADP)-ribose polymerase of DNA to both large kilobase pair fragments (30-50 and 200-300 kbp) and to nucleosomal fragments. Z-VAD.FMK also blocked all the classical ultrastructural features of apoptosis including chromatin condensation to one pole of the nucleus, nucleolar disintegration and cytoplasmic vacuolation. These results suggest the involvement of an ICE-like protease as a common mediator of apoptosis in thymocytes.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 1
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism*
  • DNA / metabolism
  • Dexamethasone / pharmacology
  • Etoposide / pharmacology
  • Flow Cytometry
  • Kinetics
  • Male
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protease Inhibitors / pharmacology
  • Rats
  • Rats, Inbred F344
  • Terpenes / pharmacology
  • Thapsigargin
  • Thymus Gland / cytology
  • Thymus Gland / drug effects
  • Thymus Gland / physiology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Protease Inhibitors
  • Terpenes
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Thapsigargin
  • Etoposide
  • Dexamethasone
  • DNA
  • Poly(ADP-ribose) Polymerases
  • Cysteine Endopeptidases
  • Caspase 1