Caspases are reversibly inactivated by hydrogen peroxide

Hydrogen peroxide (H2O2) is known to both induce and inhibit apoptosis, how ever the mechanisms are unclear. We found that H2O2 inhibited the activity of recombinant caspase-3 and caspase-8, half-inhibition occurring at about 17 muM H2O2, This inhibition was both prevented and reversed by dithiothrei tol while glutathione had little protective effect, 100-200 muM H2O2 added to macrophages after induction of caspase activation by nitric oxide or ser um withdrawal substantially inhibited caspase activity. Activation of H2O2- producing NADPH oxidase in macrophages also caused catalase-sensitive inact ivation of cellular caspases. The data suggest that the activity of caspase s in cells can be directly but reversibly inhibited by H2O2. (C) 2001 Feder ation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.