title: Single chain-urokinase binds to oxidized fibrin(ogen) derivatives.
abstract: Single chain- urokinase (scu-PA), in contrast to two chain urokinase, is a physiological plasminogen activator of fibrin selectivity. The mechanism of selective fibrinolysis of scu- PA has not been clarified up to now. This study has shown that fibrin selectivity might involve oxidative processes. Binding studies with immobilized oxidized fibrinogen degradation products (FDP) demonstrated higher affinity of scu-PA to oxidized than to unmodified FDP. The fibrin(ogen) domain responsible for this oxidant mediated increase of scu-PA affinity is localized in the D-subunit of fibrin(ogen). Thus, experimental data upon the interaction of scu-PA with fibrin(ogen) using oxidized and I- labelled fibrin(ogen) might be interpreted with caution: the oxidized product may behave in a distinct manner than the unoxidized, native, one. Activated leukocytes release large amounts of scu-PA and of oxidants of the chloramine type. The oxidants could contribute significantly to fibrinolysis and proteolysis in areas of inflammation, preparing fibrin for its specific degradation. The present data support the concept of an involvement of oxidative processes in the fibrinolytic pathway.
authors.affiliation: Department of Hematology, University Hospital Virgen del Rocío, University of Seville, Spain.
authors.forename: T W
authors.initials: TW
authors.lastname: Stief
authors.forename: E
authors.initials: E
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Digon
authors.forename: A
authors.initials: A
authors.lastname: Martin-Noya
authors.forename: R
authors.initials: R
authors.lastname: Parody
authors.forename: J M
authors.initials: JM
authors.lastname: Rodriguez
mesh_terms: D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010958:Plasminogen / Q000032:analysis; D010960:Plasminogen Activators / Q000378:metabolism*; D011485:Protein Binding; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010958:Plasminogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator