Caspases are reversibly inactivated by hydrogen peroxide.
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.
Borutaite
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Department of Biochemistry, University of Cambridge, Downing Site, Tennis Court Road, CB2 1QW, Cambridge, UK. vb207@mole.bio.cam.ac.uk
Brown
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GC
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
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