NITRIC-OXIDE INHIBITS CPP32-LIKE ACTIVITY UNDER REDOX REGULATION

The inhibitory effect of nitric oxide (NO) on the enzymatic activity o f CPP32-like proteases in the cell extract from vincristine-treated ce lls was examined in vitro. NO generated from (+/-)-(E)-methyl-2-[(E)-h ydroxyimino]-5-nitro- 6-methoxy-S-hexeneamide (NOR1) inhibited CPP32-l ike protease, which constitute a family of interleukin-1 beta-converti ng enzyme (ICE)-like proteases in a dose-dependent manner. Moreover, r ecombinant CPP32 beta activity was inhibited by NOR1 at same concentra tion. Inhibition of CPP32-like activity by NO was reversed in the pres ence of glutathione in the enzymatic reaction mixture. Thus, CPP32-lik e activity was regulated by NO under redox regulation. These findings suggest that NO may prevent apoptosis by inhibiting the ICE protease c ascade under the influence of cellular redox status. (C) 1997 Academic Press.