Nitric oxide inhibits CPP32-like activity under redox regulation.
The inhibitory effect of nitric oxide (NO) on the enzymatic activity of CPP32-like proteases in the cell extract from vincristine-treated cells was examined in vitro. NO generated from (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-S-hexen eamide (NOR1) inhibited CPP32-like protease, which constitute a family of interleukin-1beta-converting enzyme (ICE)-like proteases in a dose-dependent manner. Moreover, recombinant CPP32beta activity was inhibited by NOR1 at same concentration. Inhibition of CPP32-like activity by NO was reversed in the presence of glutathione in the enzymatic reaction mixture. Thus, CPP32-like activity was regulated by NO under redox regulation. These findings suggest that NO may prevent apoptosis by inhibiting the ICE protease cascade under the influence of cellular redox status.
Ogura
T
T
Investigative Treatment Division, National Cancer Center Research Institute East, Kashiwa, Chiba, Japan. togura@east.ncc.go.jp
Tatemichi
M
M
Esumi
H
H
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D015853:Cysteine Proteinase Inhibitors; D009574:Nitro Compounds; C101316:methyl-2-hydroxyimino-5-nitro-6-methoxy-3-hexeneamide; D009569:Nitric Oxide; D014750:Vincristine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D005978:Glutathione