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 line, by diverse stimuli including cycloheximide, thapsigargin, etoposide and staurosporine. Induction of apoptosis by all these stimuli, except etoposide, was enhanced in the presence of the trypsin-like protease inhibitor, N alpha-tosyl-L-lysinyl chloromethyl ketone (TLCK). Induction of apoptosis, assessed by morphological, flow cytometric and biochemical criteria, including proteolysis of poly(ADP-ribose) polymerase and cleavage of DNA to large kilobasepair fragments, was completely abrogated when cells were pretreated with an ICE-like protease inhibitor, Z-Val-Ala-Asp.fluoromethylketone. This suggested that an ICE homologue was a common mediator of apoptosis in THP.1 cells.
Zhu
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MRC Toxicology Unit, University of Leicester, UK.
Fearnhead
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Cohen
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D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004247:DNA / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000201:enzymology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism / Q000494:pharmacology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D014107:Tosyllysine Chloromethyl Ketone; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D003546:Cysteine Endopeptidases; D020170:Caspase 1