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)

Epsilon aminocaproic acid, an inhibitor of plasminogen and trypsinogen activators, can decrease the severity of experimental allergic encephalomyelitis (EAE) in rats. The drug was tried because of a number of observations suggesting that neutral proteases, such as plasmin, might be chemical mediators of demyelination. The highest concentrations of plasminogen activator are found in the walls of veins and venules, around which demyelination is common in many demyelinating diseases, including MS. Indeed, the earliest lesion in MS is often demyelination with little cellular infiltration. In vitro studies have shown that neutral proteases secreted by activated macrophages selectively lyse myelin basic protein.
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PMID:The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid. 56 43

Matrix-degrading proteinases secreted by tumor cells play crucial roles in tumor cell invasion and metastasis. Serum-free conditioned media of 7 human gynecological carcinoma cell lines were examined for proteinases and their inhibitors by using gelatin zymography, reverse zymography and immunoblotting. All of three ovarian adenocarcinoma cell lines secreted urokinase-type plasminogen activator. Among them, a mucinous cystadenocarcinoma cell line also secreted tissue-type plasminogen activator, plasmin-like enzyme and trypsinogen. On the other hand, two ovarian undifferentiated carcinoma cell lines mainly secreted glatinase A or B. A choriocarcinoma cell line secreted multiple metalloproteinases in the highest amount, whereas an endometrial adenocarcinoma cell line (HEC-1) derived from an early clinical stage hardly secreted any gelatinolytic enzyme. The five high proteinases producers hardly secreted the corresponding inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)-1, -2 or plasminogen activator inhibitor-1. In contrast to these highly malignant cell lines, a poor proteinase producer, HEC-1, secreted a large amount of TIMPs. Therefore, an enhanced proteolytic tendency appears to be associated with gynecological cancer cells established from highly malignant tumors.
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PMID:Characterization of matrix-degrading proteinases and their inhibitors secreted by human gynecological carcinoma cells. 762 22

The etiology of acute pancreatitis is based on several causes, among which idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is still under debate whether alcohol as the main cause of chronic pancreatitic disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of 1901 and experimental data, it is now widely accepted that the gallstone passage into or through the terminal biliopancreatic ductal system triggers acute (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the sequential intracellular mechanisms in the pathogenesis of acute pancreatitis remain unclear. A co-localization hypothesis has been proposed to explain the premature intracellular activation of trypsinogen to trypsin: due to a yet unknown defect in the intracellular protein transport and sorting system within the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation can occur. In addition, alterations of exo- and endocytosis at the apical pole exist (i.e. secretion block). The pathophysiological events are characterized by local and systemic hypovolemia and (micro)circulatory failure aggravating necrosis, followed by ARDS, renal failure and several other severe complications (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2) and kinins plays a major role as mediating factor in severe cases, resulting in multiorgan failure.
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PMID:[Etiology, pathogenesis and pathophysiology of acute pancreatitis]. 928 10

Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.
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PMID:Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. 1452 51

C-reactive protein remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinical-physiological scores and CRP provide good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data that support the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than 7 and IL-6 at the time of admission, and urine TAP, urine trypsinogen-2, and serum PMN elastase at 24 hours (Table 4). These markers only will be able to help the clinician's predictive ability if they can be performed locally and if the results can be available ina timely manner. Future research should focus on promising markers such as procalcitonin, IL-8, IL-I ra, sTNFR, CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last 15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward.
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PMID:Predictors of severity and necrosis in acute pancreatitis. 1552 23

To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.
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PMID:Inflammatory markers of disease severity in acute pancreatitis. 1574 30