Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental pancreatitis was induced in rats by intraductal injection of 0-4% Na-taurocholate. After 0-21 days the glands were removed and amylase, trypsin and chymotrypsin were measured in pancreatic homogenates. The enzyme activities decreased within 48 h to 5-20% of the control values. When 0-1% Na-taurocholate was used, the values tended to increase after 10-21 days. In pancreatic tissue, 12 h after induction of pancreatitis a 'pancreatitis-associated protein' (PAP) was found, which persisted for 4-7 days. A correlation could be found between the severity of pancreatitis and the amount of PAP in pancreatic homogenates.
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PMID:Pancreatitis-associated protein in bile acid-induced pancreatitis of the rat. 242 59

Pancreatic duct occlusion is known to produce a sustained increase in the plasma cholecystokinin (CCK) concentration and to affect the tissue content of CCK in the rat. The tissue content of CCK is correlated with regenerative changes in the pancreas after pancreatic duct occlusion. In the present study, we examined the changes in mRNA levels of pancreatic secretory trypsin inhibitors (PSTIs), pancreatitis-associated protein (PAP), and amylase in the pancreas in comparison with changes in CCK and secretin mRNA levels in the intestine and the histological changes produced by pancreatic duct ligation. Rats with an internal bile fistula and with obstruction of pancreatic flow were prepared and were sacrificed 1, 3, 7, 10, 14, and 28 days later. Then mRNA levels of CCK, secretin, PSTIs, PAP, and amylase were determined by slot-blot analysis. The CCK mRNA level gradually increased to a peak on day 10, was slightly lower on day 14, and returned to the control level on day 28. The level of secretin mRNA did not change. The mRNA levels of PSTIs increased significantly on day 3 after occlusion. PAP mRNA was detectable on days 1 and 3, being maximal on day 1. The mRNA level of amylase was markedly decreased on days 1 and 3, then remained lower than the control level. Histological examination showed acute inflammatory changes in the pancreas on days 1 and 3 and regenerative changes from day 7. These results suggest that a change in gene expression of PAP reflects acute inflammatory changes in the pancreas most sensitively.
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PMID:Changes in gene expression of pancreatitis-associated protein and pancreatic secretory trypsin inhibitors in experimental pancreatitis produced by pancreatic duct occlusion in rats: comparison with gene expression of cholecystokinin and secretin. 747 71

Neonatal screening of cystic fibrosis (CF) is presently based on immunoreactive trypsin (IRT) assay in blood spots, whose low specificity is a matter of concern. Because the pancreatitis-associated protein (PAP) proved to be a better serum marker of pancreatic alteration than exocrine enzymes, it might be an interesting alternative for CF screening. We report here a preliminary evaluation of the PAP test, conducted in retrospect on blood spots from groups of neonates already screened for CF with the IRT. Neonates with elevated IRT were submitted to subsequent analysis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Neonates with normal IRT (n = 990) or high IRT but normal genotype (n = 28) had normal PAP. Elevated PAP was observed in all CF neonates (n = 11). False-positives for the PAP test were found only among neonates with high IRT and heterozygotes for a mutation in the CFTR gene (6 out of 17 cases). That group represents less than 0.2% of newborns. These results therefore suggest that PAP discriminates CF neonates with a significantly better specificity than IRT.
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PMID:The pancreatitis-associated protein (PAP). A new candidate for neonatal screening of cystic fibrosis. 752 91

Acute pancreatitis is a rather common abdominal disorder. In most patients the disease is mild, but about 20% of cases develop a severe necrotizing form of the disease with complications. In an emergency setting, the diagnosis of acute pancreatitis remains problematic and several patients with severe disease are diagnosed only at autopsy. Measurements of amylase or lipase are the principal laboratory methods for diagnosing acute pancreatitis. However, their sensitivity and specificity are generally considered unsatisfactory. Recent advances in the knowledge of the pathogenesis of acute pancreatitis and advances in laboratory technology have revealed new diagnostic possibilities. Especially assays based on trypsin pathophysiology have brought new alternatives for diagnostics and severity grading of the disease. Additionally, development of phospholipase A2 determinations and discovery of a new pancreatic protein, pancreatitis-associated protein, are very interesting. This article summarizes the value of new methods in the laboratory diagnostics of acute pancreatitis.
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PMID:Advances in the laboratory diagnostics of acute pancreatitis. 966 95

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
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PMID:A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. 1127 30

Secretory stress proteins (SSP) are a family of proteins including isoforms of pancreatitis-associated protein (PAP) and pancreatic stone protein (PSP/reg). In vitro exposure to trypsin results in the formation of insoluble fibrillar structures. SSP are constitutively secreted into pancreatic juice at low levels. The WBN/Kob rat is a model for chronic pancreatitis, displaying focal inflammation, destruction of the parenchyma and changes in the architecture of the acinar cell; the synthesis and secretion of SSP are also increased. We have investigated the secretory apparatus by SSP immunohistochemistry at the light- and electron-microscopical (EM) levels. Immunocytochemistry of PSP/reg in Wistar control rats reveals low levels, with individual acinar cells exhibiting high immunoreactivity in zymogen granules. PAP is not detectable. In the WBN/Kob rat, PSP/reg and PAP immunoreactivity is markedly increased. Double immunofluorescence for PSP/reg and PAP I or II demonstrates that these proteins colocalize to the same cell. Acinar cells change their secretory architecture by fusion of zymogen granules and elongation of the fused organelles. The immunogold technique has demonstrated an increase of SSP in zymogen granules in WBN/Kob rats. PSP/reg-positive zymogen granules fuse to form elongated structures with fibrillar contents. An extensive PSP/reg-positive fibrillar network is established in the cytosol. Extracellular fibrils have been observed in several ductules. Thus, SSP-derived fibrils form concomitantly with acinar damage in the WBN/Kob rat. Based on the known tryptic cleavage site of SSP, the in vivo generation of fibrils is presumably the result of premature trypsin activation.
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PMID:Secretory apparatus assessed by analysis of pancreatic secretory stress protein expression in a rat model of chronic pancreatitis. 1276 8

PAP (pancreatitis-associated protein) is a 16 kDa lectin-like protein, which becomes robustly up-regulated in the pancreatic juice during acute pancreatitis. Trypsin cleaves the N-terminus of PAP, which in turn forms insoluble fibrils. PAP and its paralogue, the pancreatic stone protein, induce bacterial aggregation and, more recently, PAP was shown to bind to the peptidoglycan of Gram-positive bacteria and exert a direct bactericidal effect. However, the role of N-terminal processing in the antibacterial function of PAP has remained unclear. In the present study, we demonstrate that N-terminal cleavage of PAP by trypsin at the Arg37-Ile38 peptide bond or by elastase at the Ser35-Ala36 peptide bond is a prerequisite for binding to the peptidoglycan of the Gram-positive bacterium Bacillus subtilis. The tryptic site in PAP was also efficiently cleaved by nprE (extracellular neutral metalloprotease) secreted from B. subtilis. Trypsin-mediated processing of PAP resulted in the formation of the characteristic insoluble PAP species, whereas elastase-processed PAP remained soluble. N-terminally processed PAP induced rapid aggregation of B. subtilis without significant bacterial killing. The bacteria-aggregating activities of trypsin-processed and elastase-processed PAP were comparable. In contrast with previous reports, the Gram-negative Escherichia coli bacterium was not aggregated. We conclude that N-terminal processing is necessary for the peptidoglycan binding and bacteria-aggregating activity of PAP and that trypsin-processed and elastase-processed forms are functionally equivalent. The observations also extend the complement of proteases capable of PAP processing, which now includes trypsins, pancreatic elastases and bacterial zinc metalloproteases of the thermolysin type.
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PMID:Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation. 1925 8

Pancreatic stone protein (PSP; reported in 1979), pancreatitis-associated protein (PAP; 1984) and regenerating protein (Reg I; 1988) were discovered independently in the fields of the exocrine (pancreatitis) and endocrine (diabetes) pancreas. Subsequent analysis revealed that PSP and Reg I are identical and PAP belongs to the same protein family. PSP/Reg I and PAP share a selective and specific trypsin cleavage site and result in insoluble fibrils (PTP, PATP). Search for a functional role of PSP had led to the idea that it might serve as an inhibitor in pancreatic stone formation and PSP was renamed lithostathine. Inhibitory effects of lithostathine in stone formation have been questioned. Evidence so far obtained can support a lithogenic role rather than a lithostatic role of PSP. PAP and its isoforms have been investigated mainly regarding responses to inflammation and stress. Reg I and its isoforms have been examined on regeneration, growth and mitogenesis in gastrointestinal neoplastic diseases as well as diabetes. Evidence obtained can be applied in the prediction of prognosis and therapy for inflammatory and neoplastic diseases.
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PMID:Pancreatic stone protein/regenerating protein family in pancreatic and gastrointestinal diseases. 2180 74