Disease relevance of PLG

• The incidence of these hereditary disorders in our 204 patients (106 males and 98 females) with venous thromboembolism were 4% (three cases deficient in PC, three in PS, two in PLG, and one patient in AT III) [1].
• The early activation of plasmin by endotoxin may prevent thrombosis, and the increase in fibrinolysis is then offset by the release of plasminogen activator inhibitor [2].
• Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study [3].
• Thus, it appears that there is an imbalance between plasminogen activators and their inhibitors in colonic neoplasia in favor of u-PA, which may contribute to plasmin-mediated growth, invasiveness, and metastasis [4].
• Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator [5].

Psychiatry related information on PLG

• The results further identify and define the contribution and role of the plasminogen receptor, Ann-II, in the ethanol-induced mechanism of increased EC fibrinolysis that may underlie and contribute, in part, to the cardioprotective benefit associated with moderate alcohol consumption [6].
• Complexing of tissue plasminogen activator with PAI-1, alpha 2-macroglobulin, and C1-inhibitor: studies in patients with defibrination and a fibrinolytic state after electroshock or complicated labor [7].
• The aim of this controlled randomised clinical trial was to investigate the effects of regular low to moderate intensity physical activity on plasminogen activator inhibitor-1 (PAI-1) activity during three years while taking into account the 4G/5G polymorphism in the promoter of the PAI-1 gene [8].
• Decreased plasminogen activator inhibitor-1 activity in newly diagnosed type 2 diabetic patients following dietary modification [9].
• Excessive urokinase-type plasminogen activator activity in the euglobulin fraction of patients with Alzheimer-type dementia [10].

High impact information on PLG

• In addition, ion channels may be involved in the regulation of the traffic of macromolecules by endocytosis, transcytosis, the biosynthetic-secretory pathway, and exocytosis, e.g., tissue factor pathway inhibitor, von Willebrand factor, and tissue plasminogen activator [11].
• We assessed whether coronary stenting combined with the blockade of platelet glycoprotein IIb/IIIa receptors produces a greater degree of myocardial salvage than fibrinolysis with an accelerated infusion of alteplase, a tissue plasminogen activator, in patients with acute myocardial infarction [12].
• CONCLUSIONS: In patients with acute myocardial infarction, coronary stenting plus abciximab leads to a greater degree of myocardial salvage and a better clinical outcome than does fibrinolysis with a tissue plasminogen activator [12].
• Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investigators [12].
• METHODS: Using data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, we identified 22,361 patients with acute myocardial infarction who had an uncomplicated course for 72 hours after thrombolysis [13].

Chemical compound and disease context of PLG

• Domain 1 of the urokinase-type plasminogen activator receptor is required for its morphologic and functional, beta2 integrin-mediated connection with actin cytoskeleton in human microvascular endothelial cells: Failure of association in systemic sclerosis endothelial cells [14].
• We isolated a novel protease that converts plasminogen to angiostatin-like fragments (BL-angiostatins) from a culture of Bacillus megaterium A9542 through a single-step chromatography on CM-cellulose [15].
• Retinoic acid-enhanced invasion through reconstituted basement membrane by human SK-N-SH neuroblastoma cells involves membrane-associated tissue-type plasminogen activator [16].
• To test this suggestion, we expressed in E. coli the alphaC-fragment (residues Aalpha221-610) corresponding to the entire alphaC-domain as well as its NH(2)- and COOH-terminal halves (residues Aalpha221-391 and Aalpha392-610) and tested their effects on activation of Pg and their interaction with Pg and tPA [17].
• Plasminogen activator inhibitor 2 and urokinase-type plasminogen activator in plasma and leucocytes in patients with severe sepsis [18].

Biological context of PLG

• 125I-PLG bound to HUVEC with an estimated Kd of 310 +/- 235 nM (S.E.); each cell contained 1,400,000 +/- 1,000,000 (S.E.) binding sites [19].
• Functional studies demonstrated that HUVEC-bound PLG is activatable by TPA according to Michaelis-Menten kinetics (Km, 5.9 nM) [19].
• These findings suggest that annexin II-mediated co-assembly of t-PA and PLG may promote plasmin generation and play a key role in modulating fibrinolysis on the endothelial surface [20].
• DATA SOURCES: The MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, lanoteplase, and tenecteplase [21].
• Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2 [22].

Anatomical context of PLG

• Binding of PLG to endothelial cells may play a pivotal role in modulating thrombotic events at the vessel surface [19].
• PLG bound at an intermediate level to human fibroblasts, poorly to human smooth muscle cells, and not at all to bovine smooth muscle or bovine endothelial cells; unrelated proteins such as human albumin and IgG failed to bind HUVEC [19].
• The above findings showed human umbilical vein endothelial cells (HUVECs) treated with sense or missense oligonucleotides indicated no significant change in binding of t-PA and PLG [23].
• The production of plasminogen activators, their inhibitors and urokinase receptor by subcutaneous tumors corresponded with the production by the parental cell lines in vitro [24].
• Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts [25].

Associations of PLG with chemical compounds

• Binding of PLG was 70-80% inhibited by 10 mM epsilon-aminocaproic acid, suggesting that it is largely mediated by the lysine-binding sites of PLG [19].
• Of the ligands of HPRG tested, mesoheme (20 microM) but not heparin (M(r) 10,000, 10 microM) inhibits the formation of the HPRG-PLG complex [26].
• Urokinase didn't bind to Ann-II, demonstrating the role of receptor-related lysine residues on activation of PLG, showing that the Ann-II-PLG interaction was dependent upon carboxyl-terminal lysine residues [20].
• This was followed by a marked increase in clot-bound plasminogen having glutamic acid as NH2-terminal (glu-plasminogen) and gluplasmin. t-PA-induced enhancement of glu-plasminogen uptake appears to be mediated by plasmin but does not require the conversion of glu-plasminogen to plasminogen having lysine or methionine as NH2-terminal [27].
• The accumulation of plasminogen was faster and greater on noncrosslinked plasma clots than on clots which had been crosslinked by Factor XIIIa [27].

Physical interactions of PLG

• Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein [28].
• Plasminogen bound to a site on the TF apoprotein that appears to be distinct from the binding site for factors VII and VIIa as judged by a combination of biosensor and cell assays [29].
• The increased amount of bound Plg was demonstrated to result in a similar increase in the amount of plasmin generated from the complexes by TPA [30].
• Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin) [31].
• Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein [32].

Enzymatic interactions of PLG

• Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin [33].
• Because uPA cleaves Plg into plasmin, which activates matrix metalloproteinases (MMP), the end result was an increase in MMP activity [34].
• We have previously demonstrated that a synthetic peptide derived from amino acids 2091-2108 of the laminin A chain (designated LamA2091-2108) can significantly enhance t-PA-catalyzed Pg activation [35].
• Furthermore, human casein enhanced t-PA-catalyzed plasminogen activation, comparable to the enhancing effect obtained with fibrinogen fragments [36].
• MMP-9 cleaves plasminogen to generate a 42-kDa fragment with the N-terminal sequence PVVLLPNVE, 1 residue upstream of the MMP-7 cleavage site [37].

Co-localisations of PLG

• S100A10 also colocalizes plasminogen with the uPA-uPAR complex thereby localizing and stimulating uPA-dependent plasmin formation to the surface of cancer cells [38].

Regulatory relationships of PLG

• Plasminogen bound to the latter site on fibrin was activated by t-PA and therefore is involved in the ternary complex [39].
• Evidence is provided that in ECM, procoagulant thrombin may promote plasminogen activator activity by inactivating PAI-1 [40].
• TF enhanced two-chain urokinase (tcuPA) activation of Glu-plasminogen, but not of miniplasminogen, in a dose-dependent, saturable manner (half maximal stimulation at 59 pmol/L) [29].
• Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cells [41].
• Our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-PA-, and in some cases also via a factor XII-, dependent pathway [42].

Other interactions of PLG

• HRGP covalently cross-linked to Sepharose 4B simultaneously bound both 125I-TSP and 131I-Plg, confirming trimolecular complex formation [28].
• Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator [43].
• We have studied the distribution of the plasminogen activator inhibitor type 1 (PAI-1) in cultures of confluent human umbilical vein endothelial cells [44].
• Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets [45].
• The stimulatory effect of TF on plasminogen activation was confirmed when plasmin formation was examined directly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis [29].

Analytical, diagnostic and therapeutic context of PLG

• We now report the binding of human PLG to cultured human umbilical vein endothelial cell (HUVEC) monolayers, utilizing a newly devised cell monolayer enzyme-linked immunosorbent assay system [19].
• Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction [46].
• Rocket immunoelectrophoresis of mixtures of the purified radiolabeled proteins into anti-Plg containing agarose also confirmed trimolecular complex formation [28].
• Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models [47].
• Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation [48].

References