Involvement of multiple proteases during Fas-mediated apoptosis in T lymphocytes.
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.
Chow
S C
SC
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Weis
M
M
Kass
G E
GE
Holmström
T H
TH
Eriksson
J E
JE
Orrenius
S
S
D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020170:Caspase 1; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002474:Cell-Free System; D003374:Coumarins / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D049934:Isocoumarins; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D019014:fas Receptor
D000954:Antigens, Surface; D003374:Coumarins; D049934:Isocoumarins; D019014:fas Receptor; D014108:Tosylphenylalanyl Chloromethyl Ketone; C046235:3,4-dichloroisocoumarin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D020170:Caspase 1