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 th at the protease inhibitors N-alpha-tosyl-L-lysinyl-chloromethylketone (TLCK) and benzyloxycarbonyl-valinyl-alaninyl-aspartyl fluoromethylket one (Z-VAD.FMK) inhibit apoptosis. N-tosyl-L-phenylalaninyl-chlorometh ylketone (TPCK) has a very different effect, inducing the early morpho logical and biochemical changes associated with apoptosis. TLCK inhibi ts trypsin-like proteases whilst Z-VAD.FMK inhibits interleukin-1 beta -converting enzyme (ICE)-like proteases; this and the contrasting effe cts of TPCK support the hypothesis that thymocyte apoptosis involves a hierarchy of proteases which act at different stages of the process.