Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated phagocytes (especially polymorphonuclear granulocytes (PMNs)) by respiratory oxidative/photonic burst (activation of NADPH-oxidase and myeloper-oxidase) generate large amounts of oxidants of the hypochlorite-/chloramine-type, which are physiologic sources for singlet oxygen (1O2), a nonradical-excited (photon (h nu) emitting) oxygen species [Weiss SJ, NEJM 1989;320:365-376]. In vitro experiments show that 1O2 (1) inhibits coagulation by inactivation of thrombocytes, fibrinogen, factor V, factor VIII, and factor X and (2) activates fibrinolysis by inactivation of the main fibrinolysis inhibitors plasminogen activator inhibitor (PAI)-1 and alpha-2-antiplasmin, and by activation of single-chain urokinase by plasmin and oxidized fibrin. Additionally, this work suggests that 1O2/h nu acts antithrombotically, inducing selective thrombolysis in vivo (i.e., thrombolysis induced by 0.1 to 0.5 mmol/l chloramine within 30 to 60 minutes without changes of the plasmatic hemostasis system). 1O2 might activate flowing to (on the endothelium) rolling PMN, increasing their chance to get in contact with fibrin/platelet aggregates deposited on the endothelial layer. Via 1O2 generation, the thrombus-activated phagocytes might call for (acute, physiologic) inflammation/fibrinolysis amplification, resulting in the "moving front" of PMN, which infiltrates and destroys the thrombus. 1O2 seems to (partially) participate in the reactivity of nitric oxide, another prooxidative agent. The inhibition of physiologic amounts of 1O2 by blood cholesterol might be involved in the pathogenesis of atherothrombosis. Consequently, it is suggested that activated PMNs modulate hemostasis, shifting it into an antithrombotic state; this cellular part of fibrinolysis seems to be of greater physiologic importance than the plasmatic one. Impaired PMN function (e.g., as occurring in patients with antineutrophil cytoplasmic antibodies or under cytostatic treatments) often results in serious thrombotic complications. Light is the only signal whose origin can be immediately recognized by a fast moving cell in the (dark) blood stream. The cell signal action of 1O2/h nu (e.g., released by chloramines such as taurine-chloramine or vancomycin, by fiberoptic, by photodynamic therapy, or by so-called redox-cycling drugs such as quinones or tetracyclines) might be a new and physiologic principle for pharmacologic intervention in atherothrombosis.
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PMID:The antithrombotic factor singlet oxygen/light (1O2/h nu). 1072 45

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor that activates phagocytic NADPH-oxidase. The effect of HP-NAP on the production of tissue factor (TF), plasminogen activator inhibitor-2 (PAI-2), and urokinase-type plasminogen activator (u-PA) by human blood mononuclear cells (MNC) was evaluated by using functional and immunological assays and mRNA analysis. HP-NAP induced time- and dose-dependent increases in TF and PAI-2, with a maximal effect at 300 nmol/L (>15-fold increase in antigens). No changes in u-PA were observed. When whole bacteria were used, an H. pylori mutant lacking HP-NAP was significantly less active than the wild-type strain. MNC from a patient with chronic granulomatous disease behaved as do normal cells, which indicates that HP-NAP effects can occur independently of NADPH-oxidase. HP-NAP, by inducing the coordinate expression of cell procoagulant and antifibrinolytic activities, might favor fibrin deposition and contribute to the inflammatory reaction of gastric mucosa elicited by H. pylori.
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PMID:Helicobacter pylori neutrophil-activating protein stimulates tissue factor and plasminogen activator inhibitor-2 production by human blood mononuclear cells. 1123 30