Regulation of cathepsin K activity by hydrogen peroxide.
Although cysteine cathepsins, including cathepsin K, are sensitive to oxidation, proteolytically active forms are found at inflammatory sites. Regulation of cathepsin K activity was analyzed in the presence of H2O2 to gain an insight into these puzzling observations. H2O2 impaired processing of procathepsin K and inactivated its mature form in a time- and dose-dependent mode. However, as a result of the formation of a sulfenic acid, as confirmed by trapping in the presence of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazol, approximately one-third of its initial activity was restored by dithiothreitol. This incomplete inactivation may partially explain why active cysteine cathepsins are still found during acute lung inflammation.
Godat
Emmanuel
E
INSERM, U 618, Protéases et Vectorisation Pulmonaires, and IFR 135 Imagerie Fonctionnelle, Université François Rabelais, Faculté de Médecine, 10 Bd Tonnellé, F-37032 Tours cedex, France.
Hervé-Grvépinet
Virginie
V
Veillard
Florian
F
Lecaille
Fabien
F
Belghazi
Maya
M
Brömme
Dieter
D
Lalmanach
Gilles
G
D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D013053:Spectrophotometry
D006861:Hydrogen Peroxide; D002403:Cathepsins; C118659:procathepsin K; D056657:Cathepsin K