title: Caspases are reversibly inactivated by hydrogen peroxide.
abstract: Hydrogen peroxide (H2O2) is known to both induce and inhibit apoptosis, however the mechanisms are unclear. We found that H2O2 inhibited the activity of recombinant caspase-3 and caspase-8, half-inhibition occurring at about 17 microM H2O2. This inhibition was both prevented and reversed by dithiothreitol while glutathione had little protective effect. 100-200 microM H2O2 added to macrophages after induction of caspase activation by nitric oxide or serum withdrawal substantially inhibited caspase activity. Activation of H2O2-producing NADPH oxidase in macrophages also caused catalase-sensitive inactivation of cellular caspases. The data suggest that the activity of caspases in cells can be directly but reversibly inhibited by H2O2.
authors.affiliation: Department of Biochemistry, University of Cambridge, Downing Site, Tennis Court Road, CB2 1QW, Cambridge, UK. vb207@mole.bio.cam.ac.uk
authors.forename: V
authors.initials: V
authors.lastname: Borutaite
authors.forename: G C
authors.initials: GC
authors.lastname: Brown
mesh_terms: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry* / Q000187:drug effects; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D003374:Coumarins / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004229:Dithiothreitol / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry* / Q000187:drug effects; D013050:Spectrometry, Fluorescence
chemical_list: D003374:Coumarins; D016895:Culture Media, Serum-Free; D020030:Nitric Oxide Donors; D009842:Oligopeptides; D016877:Oxidants; D011994:Recombinant Proteins; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; D006861:Hydrogen Peroxide; D002374:Catalase; D019255:NADPH Oxidases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D005978:Glutathione; D004229:Dithiothreitol