Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have described the intracellular type of platelet-activating factor acetylhydrolase (PAF-AH) in the membrane extract of human red blood cells (RBCs). The enzymatic activity was inhibited by diisopropylfluorophosphate, trypsin or pronase E, but not affected by EDTA or the addition of 1-O-hexadecyl-2-hexadecanoyl-rac-glycero-3-phosphocholine or 1-O-hexadecyl-2-[(cis)-9-octadecenoyl]-rac-glycero-3-phosphocholin e. The activity in 10 healthy volunteers was 3.89 +/- 3.26 pmol/10(9) RBCs/min (or 148 +/- 73 nmol/g protein/min) (mean +/- SD). Since PAF-AH is also known to hydrolyze oxidized derivatives of phosphatidylcholine and since RBCs are not effector cells of PAF, the observed activity in RBC membranes may play a potential role in degrading oxidation products of membrane phospholipids.
...
PMID:Activity of platelet-activating factor acetylhydrolase exists in red cell membrane. 156 49

The role of blood platelets in the disturbed haemostasis in acute pancreatitis is not fully elucidated. The aim of this study was to evaluate the blood platelet function during the first hours of acute experimental pancreatitis (AEP) in dogs. AEP was induced by the retrograde injection of bile and trypsin into the main pancreatic duct. Platelet count, platelet aggregation induced with ADP, PAF, AA as well as plasma Beta-TG and TXB2 levels were determined. At 30 min after induction of AEP a significant decrease of platelet count was noted; these changes were observed until 4 th hr. At 30 min as well as at 60 min of AEP increased sensitivity of platelet aggregation to ADP was found. After that time evident decrease of platelet aggregation to ADP was shown. Platelets sensitivity to PAF was higher at 30 min of AEP whereas 60 min, 2 and 4 hrs after AEP normalization of platelet aggregation by PAF was observed. The significant increase of plasma Beta-TG and TXB2 concentrations corresponded well to changes of platelet aggregation. These results indicate that AEP affects blood platelet function with the drop of their count.
...
PMID:Does acute experimental pancreatitis affect blood platelet function? 252 19

Although a great deal has been learned about the mediators produced by mast cells, the ultimate biologic function(s) of mast cell remains a mystery. Histamine, LTC4, PAF, and possibly tryptase (C3a generation) all enhance vasopermeability. Mediators with anticoagulant activities such as heparin and tryptase (fibrinogenolysis) and antithrombotic activity, PGD2, would appear to facilitate dispersion in tissues of the plasma ultrafiltrate brought there by the subgroup of mediators that enhance vasopermeability. In contrast, PAF causes platelet aggregation and chymase may cause arteriolar vasoconstriction (decreasing the volume of plasma reaching venules) by generation of angiotensin II. Assessment of any differential production of mediators by different types of mast cells will be of obvious importance in sorting out the physiologic responses to mast cell activation as well as the pathophysiology of allergic reactions.
...
PMID:Mediators of human mast cells and human mast cell subsets. 310 66

The structure of the potent inflammatory mediator, platelet-activating factor, is 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC, PAF-acether). Human sera contain an acid labile factor (ALF) that is a Ca+2-independent 2-acylhydrolase-specific for AGEPC and AGEPC-like molecules. The enzyme functions by catalytically removing the sn-2 acetyl moiety from AGEPC, producing the biologically inactive sn-2 hydroxy form or 2-lyso-GEPC. Incubation of ALF with sn-2 acyl PAF analogs indicated that the enzyme hydrolyzes the sn-2 fatty acid only if the chain length is five carbons or less, the sn-1 position fatty acid length is greater than 10 carbon units, and at least one methyl group is present on the terminal amine of the choline group. The enzyme was active with either an ether or ester linkage at the sn-1 position. ALF is inactivated by heating to 65 degrees C for 30 min. It is pronase and trypsin sensitive but resistant to papain and papain with dithiothreitol. Further characteristics of human ALF indicated a broad pH range of activity with an optimum of pH 6.2 and an isoelectric point of 6.2 to 6.7. The specificity and Ca+2 independence of human ALF sets it apart from phospholipase A2. It is proposed that human ALF be called human serum PAF-acylhydrolase to distinguish it from other hydrolases currently known to exist.
...
PMID:Substrate specificity and partial characterization of the PAF-acylhydrolase in human serum that rapidly inactivates platelet-activating factor. 351 60

Since proteolytic enzymes play a key role in endotoxaemia and anaphylaxis, diseases in which PAF-acether may be involved, we have investigated the activity of BN 52021 and BN 52063, two potent and specific PAF-acether antagonists, on plasma protease activity in the rat. After oral administration, both drugs dose-dependently decreased plasma trypsin-like activity (PTLA) although they did not show any inhibitory effect in vitro. PAF-acether and endotoxin injected into rats increased PTLA, the increase with endotoxin appearing more slowly but to a higher extent than with PAF-acether. Inhibition of the endotoxin-induced increase in PTLA was obtained with BN 52021, BN 52063 and dexamethasone, whereas aprotinin was ineffective. Since BN 52021 and BN 52063 reduced also the endotoxin-induced lethality in the rat, their antiprotease activity may be a consequence of their PAF-antagonistic effect. Further studies will be required with other PAF antagonists to assess fully this assumption.
...
PMID:Inhibition of rat endotoxin-induced lethality by BN 52021 and BN 52063, compounds with PAF-acether antagonistic effect and protease-inhibitory activity. 359 54

FWPs are usually stable for several months. However, in less than a week, one lot of FWPs lost its ability to aggregate with bovine PAF or human vWF plus ristocetin. Initial experiments suggested that the loss of aggregability was caused by contamination of the FWPs with an extracellular protease of Serratia marcescens. Highly purified protease preparations from the culture filtrates of S. marcescens (SP), as well as from two strains of Pseudomonas aeruginosa, destroyed the aggregability of FWPs as a function of time and concentration. On the basis of azocasein units, the SP was found to be at least eight times more potent against FWPs as a substrate than either of the P. aeruginosa proteases. The effect of SP on FWP aggregability was inhibited by prior EDTA treatment and was restored by addition of Zn2+ in slight molar excess. Purified PAF, but not dilutions of bovine plasma, lost all PAF activity when incubated with SP. SP-treated FWPs would still aggregate with 10 microgram/ml polylysine. SP digestion of FWPs was more selective than digestion with trypsin or chymotrypsin, on the basis of both the polyacrylamide gel electrophoresis pattern and the amount of protein in the platelet digest supernatant. SP does not aggregate fresh washed platelets or initiate the release reaction but renders them unaggregable with vWF. SP and related proteases may be useful in the study of platelet membranes.
...
PMID:The effect of extracellular proteases from gran-negative bacteria on the interaction of von Willebrand factor with human platelets. 678 Jun 41

We examined the production of PAF, a mediator of shock, and LysoPAF, an inactive metabolite of PAF, in the guinea pig peritoneal cavity after i.p. administration of Escherichia coli LPS. Within 1 h of LPS administration, the level of PAF in the peritoneal fluid increased from 4.9 to 37.2 pmol/animal and decreased to the control value thereafter. In contrast, the level of lysoPAF gradually rose from 63.5 to 268 pmol/animal for up to 6 h. The activity of acetylhydrolase, which converts PAF to lysoPAF, in the peritoneal cavity increased in parallel with the increase in the lysoPAF level. The enzyme was distinguishable from phospholipase A2, because p-bromophenacylbromide (p-BPB), Ca2+, and ethylenediaminetetraacetic acid (EDTA) did not affect its enzymatic activity. In addition, this acetylhydrolase revealed similar biochemical properties to that detected in plasma. Both acetylhydrolases were resistant to trypsin treatment and had the same apparent molecular weight, as shown by gel-filtration column chromatography. These results suggest that the acetylhydrolase, which accumulates in the peritoneal cavity, infiltrates from the plasma in response to LPS, and then participates in the exclusion of PAF during endotoxin shock.
...
PMID:Accumulation of platelet-activating factor acetylhydrolase in the peritoneal cavity of guinea pig after endotoxin shock. 782 56

General anesthetics and radiocontrast media (RCM) can cause anaphylactic or anaphylactoid reactions. These are usually underdiagnosed and underreported, but their incidence is apparently rising. Their pathogenesis is complex and not completely understood, but the release of vasoactive mediators from basophils and mast cells plays a central role. The recent development of in vitro techniques to study the release of preformed (histamine and tryptase) and de novo synthesized mediators (PGD2, LTC4, and PAF) from purified basophils and mast cells has made it possible to quantify the mediator-releasing activity of anesthetics such as muscle relaxants, general anesthetics, opioids, and benzodiazepines and RCM on human basophils and mast cells isolated from lung, skin and heart tissues. The majority of general anesthetics and RCM tested induced only the release of preformed mediators (histamine and tryptase), not of the de novo synthesized eicosanoids. There was wide variability in the response of basophils and mast cells from different donors to the same drug or RCM, presumably due to the releasability parameter. Hyperosmolality is probably not the only factor responsible for basophil and mast cell activation by RCM. The in vitro release of histamine induced by anesthetic drugs and RCM was correlated with the release of tryptase. Given the longer half-life of tryptase than histamine in plasma, measurements of plasma tryptase may become a useful diagnostic tool for identifying adverse reactions to anesthetics and RCM.
...
PMID:Role of mast cells, basophils and their mediators in adverse reactions to general anesthetics and radiocontrast media. 864 73

The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer.
...
PMID:Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer. 898 54

In the present work we review the existing evidence for a LPS-induced cytokine-mediated eosinophil accumulation in a model of acute inflammation. Intrathoracic administration of LPS into rodents (mice, rats or guinea pigs) induces a significant increase in the number of eosinophils recovered from the pleural fluid 24 hr later. This phenomenon is preceded by a neutrophil influx and accompanied by lymphocyte and monocyte accumulation. The eosinophil accumulation induced by LPs is not affected by inhibitors of cyclo or lipoxygenase nor by PAF antagonists but can be blocked by dexamethasone or the protein synthesis inhibitor cycloheximide. Transfer of cell-free pleural wash from LPS injected rats (LPS-PW) to naive recipient animals induces a selective eosinophil accumulation within 24 hr. The eosinophilotactic activity present on the LPS-PW has a molecular weight ranging between 10 and 50 kDa and its effect is abolished by trypsin digestion of the pleural wash indicating the proteic nature of this activity. The production of the eosinophilotactic activity depends on the interaction between macrophages and T-lymphocytes and its effect can not be blocked by anti-IL-5 monoclonal antibodies. Accumulated evidence suggest that the eosinophil accumulation induced by LPS is a consequence of a eosinophilotactic cytokine produced through macrophage and T-cell interactions in the site of a LPS-induced inflammatory reaction.
...
PMID:A role for lymphocytes and cytokines on the eosinophil migration induced by LPS. 969 33


1 2 3 Next >>

---