Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hageman factor dependent pathways are influenced by several control proteins which modulate the extent of activation and biologic activity of these enzyme substrates (Fig. 1). C1 INH plays a prominent role by acting at the common initiating step for all three Hageman factor dependent systems and its deficiency produces disease in man. Alpha-2 macroglobulin appears to play an important role in the fibrinolytic sequence, having potent activity towards both plasminogen activator and plasmin. Antithrombin most prominently influences the state of activation of the coagulation sequence by regulating the enzymatic activities of activated Factors XI, IX and X and, most importantly, that of thrombin. Significantly, deficiency of antithrombin results in increased thrombosis in man.
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PMID:Plasma inhibitors of the Hageman factor dependent pathways. 79 48

Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.
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PMID:Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. 146 38

The conversion of the plasminogen proactivator to plasminogen activator by activated Hageman factor or its fragments has been recognized as an essential step in the conversion of plasminogen to plasmin. The plasminogen proactivator has been completely separated from prekallikrein and pre-PTA, two other proenzyme substrates of activated Hageman factor or its fragments. Plasminogen proactivator, free of any contaminating proteins as assessed by disc gel electrophoresis or isoelectric focusing, revealed a single band with an isoelectric point of 8.9 corresponding in position to the Hageman factor activatable material eluted from replicate unstained gels. After conversion of plasminogen proactivator by Hageman factor fragments to the plasminogen activator, the active site of the plasminogen activator is not inhibited by C1INH and is thus readily distinguished from that of kallikrein or PTA. The plasminogen activator is susceptible to inactivation by DFP while the plasminogen proactivator is not, as has been the case for esterases having a serine in the active site. Its interaction with plasminogen is inhibited by epsilon-aminocaproic acid.
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PMID:The fibrinolytic pathway of human plasma. Isolation and characterization of the plasminogen proactivator. 426 75

Severe veno-occlusive disease (VOD), characterised by elevated serum bilirubin levels, is a known complication in the first 3 weeks after peripheral blood stem cell transplantation (PBSCT). Severe VOD is associated with capillary leakage and multiple organ dysfunction and leads to high mortality. We report a 17-year-old male, who developed VOD with capillary leakage (CL) after allogeneic PBSCT. The patient presented with a maximum serum bilirubin of 25.4 mg/dl, weight gain (10% of baseline weight), generalized edema, cardiovascular insufficiency, complement activation, jaundice and a decreased AT and protein C functional activity. After VOD and CL were diagnosed the patient was treated with recombinant human plasminogen activator (rt-PA) and C1 esterase-inhibitor concentrate (C1-INH-C). The clinical symptoms resolved and the patient's status stabilized. The patient was in an adequate clinical state 5 months after transplantation. We noted that the combined therapy with rt-PA and C1-INH-C in this high-risk situation led to a resolution of VOD with CL.
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PMID:Hepatic veno-occlusive disease with severe capillary leakage after peripheral stem cell transplantation: treatment with recombinant plasminogen activator and C1-esterase inhibitor concentrate. 961 90

Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors including vascular endothelial growth factors (VEGFs), angiopoietins (ANGPTs) and phospholipase A2 enzymes (PLA2). We previously reported that patients with C1-INH-HAE in remission have increased plasma levels of VEGFs, ANGPTs and secreted PLA2. In this study, we sought to analyze plasma levels of these mediators in 15 patients with C1-INH-HAE during the acute attack compared to remission. Plasma concentrations of VEGF-A, VEGF-C and VEGF-D were not altered during attack compared to remission. Moreover, VEGF-D concentrations were not altered also in remission phase compared to controls. Concentrations of ANGPT1, a vascular stabilizer, were increased during attacks compared to symptoms-free periods, whereas ANGPT2 levels were not altered. The ANGPT2/ANGPT1 ratio was decreased during angioedema attacks. Platelet activating factor acetylhydrolase activity was increased in patients with C1-INH-HAE in remission compared to controls and was decreased during angioedema attacks. Our results emphasize the complexity by which several vasoactive mediators are involved not only in the pathophysiology of C1-INH-HAE, but also during angioedema attacks and its resolution.
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PMID:Hereditary angioedema attack: what happens to vasoactive mediators? 3184 56