AN ICE-LIKE PROTEASE IS A COMMON MEDIATOR OF APOPTOSIS INDUCED BY DIVERSE STIMULI IN HUMAN MONOCYTIC THP.1 CELLS

Apoptosis was induced in THP.1 cells, a human monocytic tumour cell li ne, by diverse stimuli including cyclo-heximide, thapsigargin, etoposi de and staurosporine. Induction of apoptosis by all these stimuli, exc ept etoposide, was enhanced in the presence of the trypsin-like protea se inhibitor, N alpha-tosyl-L-lysinyl chloromethyl ketone (TLCK), Indu ction of apoptosis, assessed by morphological, flow cytometric and bio chemical criteria, including proteolysis of poly(ADP-ribose) polymeras e and cleavage of DNA to large kilobasepair fragments, was completely abrogated when cells were pretreated with an ICE-like protease inhibit or, Z-Val-Ala-Asp . fluoromethylketone. This suggested that an ICE hom ologue was a common mediator of apoptosis in THP.1 cells.