Titre
Interaction with substrate sensitises caspase-3 to inactivation by hydrogen peroxide
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Hampton, M. B.
Auteure/Auteur
Stamenkovic, I.
Auteure/Auteur
Winterbourn, C. C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0014-5793
Statut éditorial
Publié
Date de publication
2002
Volume
517
Numéro
1-3
Première page
229
Dernière page/numéro d’article
232
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Résumé
Caspases have an active site cysteine whose oxidation blocks catalytic activity. Caspase activity, measured in lysates of apoptotic cells, was inhibited by H2O2 with an IC50 of 7 microM. Recombinant caspase-3 was directly inhibited by H2O2, with an estimated second-order rate constant of 750 M-1 s-1. These values were determined when H2O2 was added while the caspases were cleaving a peptide substrate. There was a 40-fold decrease in sensitivity to inactivation if the substrate was absent at the time of H2O2 addition. These results rationalise conflicting reports of the sensitivity of caspase-3 to H2O2, and identify a novel mechanism for sensitising a thiol enzyme to oxidative inactivation
Sujets
PID Serval
serval:BIB_73EED3EED349
PMID
Date de création
2008-01-29T17:33:16.682Z
Date de création dans IRIS
2025-05-21T00:30:23Z