DNA degradation and proteolysis in thymocyte apoptosis.
Data from a number of model systems support a role for proteolysis in apoptotic cell death. Using immature rat thymocytes, we demonstrate that the protease inhibitors N-alpha-tosyl-L-lysinyl-chloromethylketone (TLCK) and benzyloxycarbonyl-valinyl-alaninyl-aspartyl fluoromethylketone (Z-VAD.FMK) inhibit apoptosis. N-tosyl-L-phenylalaninyl-chloromethylketone (TPCK) has a very different effect, inducing the early morphological and biochemical changes associated with apoptosis. TLCK inhibits trypsin-like proteases whilst Z-VAD.FMK inhibits interleukin-1 beta-converting enzyme (ICE)-like proteases; this and the contrasting effects of TPCK support the hypothesis that thymocyte apoptosis involves a hierarchy of proteases which act at different stages of the process.
Fearnhead
H O
HO
MRC Toxicology Unit, University of Leicester, UK.
MacFarlane
M
M
Dinsdale
D
D
Cohen
G M
GM
D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000378:metabolism*; D010450:Endopeptidases / Q000502:physiology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000502:physiology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology
D014107:Tosyllysine Chloromethyl Ketone; D014108:Tosylphenylalanyl Chloromethyl Ketone; D004247:DNA; D010450:Endopeptidases