Involvement of multiple proteases during Fas-mediated apoptosis in T lymphocytes

FEBS Lett. 1995 May 8;364(2):134-8. doi: 10.1016/0014-5793(95)00370-o.

Abstract

The mechanism of Fas antigen-mediated apoptosis is at present unclear. We show here that the 100,000 x g supernatant from cell lysates prepared from anti-Fas-stimulated JUR-KAT T cells, induces chromatin fragmentation in isolated nuclei with concomitant morphological changes typically seen in apoptosis. The formation of this apoptotic nuclei promoting activity (ANPA) in JURKAT T cells after Fas antigen ligation was blocked by the serine protease inhibitors, TPCK and DCI, and by the interleukin 1-beta-converting enzyme inhibitor, VAD-FMK. In addition, chromatin degradation and morphological changes mediated by the ANPA in isolated nuclei were inhibited by TPCK, but not by DCI or VAD-FMK. These results suggest that Fas-mediated apoptosis in T cells involves the activation of a cascade of proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 1
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Cell-Free System
  • Coumarins / pharmacology
  • Cysteine Endopeptidases / metabolism
  • Endopeptidases / metabolism*
  • Humans
  • Isocoumarins
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology
  • fas Receptor

Substances

  • Antigens, Surface
  • Coumarins
  • Isocoumarins
  • fas Receptor
  • Tosylphenylalanyl Chloromethyl Ketone
  • 3,4-dichloroisocoumarin
  • Endopeptidases
  • Cysteine Endopeptidases
  • Caspase 1