title: Regulation of cathepsin K activity by hydrogen peroxide.
abstract: 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.
authors.affiliation: 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.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Godat
authors.forename: Virginie
authors.initials: V
authors.lastname: Hervé-Grvépinet
authors.forename: Florian
authors.initials: F
authors.lastname: Veillard
authors.forename: Fabien
authors.initials: F
authors.lastname: Lecaille
authors.forename: Maya
authors.initials: M
authors.lastname: Belghazi
authors.forename: Dieter
authors.initials: D
authors.lastname: Brömme
authors.forename: Gilles
authors.initials: G
authors.lastname: Lalmanach
mesh_terms: D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D013053:Spectrophotometry
chemical_list: D006861:Hydrogen Peroxide; D002403:Cathepsins; C118659:procathepsin K; D056657:Cathepsin K