A cleavage-site-directed inhibitor of interleukin-1 beta-converting enzyme-like proteases inhibits apoptosis in primary cultures of rat hepatocytes.
Apoptosis induced in primary hepatocytes by transforming growth factor beta1 and staurosporine produced chromatin condensation, DNA cleavage is detected by in situ end-labelling, field inversion and conventional gel electrophoresis, and cell detachment. These effects were abolished by benzyloxycarbonyl-valinylalanylaspartylfluoromethyl ketone, a cleavage-site-directed inhibitor of interleukin-1beta-converting enzyme-like proteases, and this finding suggests that these enzymes are involved in liver apoptosis.
Cain
K
K
MRC Toxicology Unit, Leicester, U.K.
Inayat-Hussain
S H
SH
Couet
C
C
Cohen
G M
GM
D000470:Alkaloids / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D019311:Staurosporine; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000470:Alkaloids; D000590:Amino Acid Chloromethyl Ketones; D002843:Chromatin; D015853:Cysteine Proteinase Inhibitors; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D009707:Nucleosomes; D009842:Oligopeptides; D011480:Protease Inhibitors; D016212:Transforming Growth Factor beta; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C096429:L 709049; D004247:DNA; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D019311:Staurosporine