Caspases are reversibly inactivated by hydrogen peroxide

FEBS Letters

Borutaite, Vilmante¹  Brown, Guy C¹ 

[1] Department of Biochemistry, University of Cambridge, Downing Site, Tennis Court Road, Cambridge CB2 1QW, UK

关键词: Apoptosis;    Caspase;    Hydrogen peroxide;    Macrophage;    amc;    amino-methyl-coumarin;    DMEM;    Dulbecco's modified Eagle medium;    DTT;    dithiothreitol;    GSH;    reduced glutathione;    GSNO;    S-nitrosoglutathione;    PMA;    phorbol 12-myristate 13-acetate;    ROS;    reactive oxygen species;   

DOI  :  10.1016/S0014-5793(01)02593-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM H₂O₂. This inhibition was both prevented and reversed by dithiothreitol while glutathione had little protective effect. 100–200 μM 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.

【 授权许可】

Unknown