Three inhibitors that are based upon a 4-heterocyclohexanone nucleus were synthesized and evaluated for activity against the serine protease plasmin. Inhibitors of plasmin have potential as cancer chemotherapeutic agents that act by blocking both angiogenesis and metastasis. Inhibitor 1 has moderate activity against plasmin but shows good selectivity for this enzyme compared to other serine pro...

The effect of nonenzymatic glycosylation on the susceptibility of fibrin to degradation by the specific fibrinolytic enzyme plasmin was evaluated using both a fibrin plate assay and a fluorogenic synthetic plasmin substrate assay. Data from both types of experiments demonstrate that nonenzymatic glycosylation reduces the susceptibility of fibrin to plasmin degradation. Acetylation and carbamyla...

Plasmin, the primary fibrinolytic enzyme, has a broad substrate spectrum and is implicated in biologic processes dependent upon proteolytic activity, such as tissue remodeling and cell migration. Active plasmin is generated from proteolytic cleavage of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Here, we have investiga...

The urokinase-urokinase receptor system plays a dominant role in the degradation and invasion of extracellular matrix (ECM) by tumor cells. In this system, urokinase bound to its cell receptor converts plasminogen to plasmin, a broad-spectrum serine protease that participates in the degradation and invasion of connective tissues by tumor cells. In this study, we evaluated whether these activiti...

The subcellular localization of the platelet membrane receptors glycoproteins (GP) Ib and IIb/IIIa [corrected] has been studied within resting platelets by a combination of biochemical and cytochemical techniques. While both GPIb and GPIIb/IIIa are localized within the plasma membrane and surface-connected canalicular system (SCCS) membranes, only GPIIb/IIIa is present within the internal face ...

Human α2-antiplasmin (α2AP, also called α2-plasmin inhibitor) is the main physiological inhibitor of the fibrinolytic enzyme plasmin. α2AP inhibits plasmin on the fibrin clot or in the circulation by forming plasmin-antiplasmin complexes. Severely reduced α2AP levels in hereditary α2AP deficiency may lead to bleeding symptoms, whereas increased α2AP levels have been associated with increased th...

Transforming growth factor-beta (TGF beta) is produced by most cultured cells in an inactive form. Potential activation mechanisms of latent TGF beta were studied using fibroblastic (NRK-49F and AKR-MCA) cell-conditioned medium as a model. Active TGF beta was monitored by radioreceptor and soft agar assays as well as by antibody inhibition and immunoprecipitation. Little or no TGF beta was dete...

Background. Platelet activation occurs in vivo during pharmacologic thrombolysis and may contribute to recurrent thrombosis. Plasmin does not directly activate platelets except at high concentrations; thus, the mechanisms for platelet activation during thrombolysis remain undefined. Increases in thrombin activity also occur in patients treated with fibrinolytic agents and may contribute to acti...