Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human pancreatic cDNA library was screened with the cDNA encoding rat "pancreatitis-associated protein" (PAP). The selected clone encoded a secretory protein structurally related to rat PAP. The protein had the same size as rat PAP and showed 71% amino acid identity, the six half-cystines being in identical positions. Domains of the proteins showing homologies with calcium-dependent lectins were also conserved. In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products. The human protein was therefore named human pancreatitis-associated protein (PAP-H). Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis. In that tissue, the protein could be immunolocalized to the apical regions of acinar cells. An immunoassay was also constructed to quantify the protein in serum. Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis. Values were close to background in healthy subjects and in patients with other abdominal diseases. These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as biological marker of acute pancreatitis.
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PMID:Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. 146 87

A new protein was purified from the pancreatic juice of rats with acute pancreatitis. That protein, not detectable in control animals, was called "pancreatitis-associated protein." It was first observed 6 hours after induction of experimental pancreatitis with taurocholate or cerulein, reached maximal levels of 45 micrograms/mg protein in zymogen granules and 1.8 micrograms/mg protein in pancreatic tissue during the acute phase (48 hours), and disappeared during recovery (day 5). It was never detected in spleen, liver, kidney, heart, or lung. The detection limit of the assay system was 12 ng/mg protein, so that pancreatitis-associated protein levels increased at least 100-fold in pancreatic tissue during the acute phase. The molecular weight (12,000) and isoelectric point (8.2) were determined by two-dimensional gel electrophoresis. Subcellular fractionation and immunoelectron microscopy showed that the protein was synthesized on the rough endoplasmic reticulum and stored in zymogen granules before being secreted, similar to other pancreatic secretory proteins. Immunoblotting and two-dimensional gel electrophoresis revealed that the same protein was synthesized upon induction of pancreatitis by cerulein infusion, by retrograde injection of bile acids, or pancreatitis induced by pancreatic surgery. The pancreatitis-associated protein is therefore an acute-phase protein that differs from other proteins of that family because of its exocrine nature.
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PMID:Characterization of a rat pancreatic secretory protein associated with pancreatitis. 170 29

We investigated pancreatic gene expression in the rat in response to taurocholate-induced acute pancreatitis. Concentrations of transcripts encoding pancreatic protein showed noncoordinated alterations. Contents in amylase, trypsinogen I, chymotrypsinogen B, elastase 1, and procarboxypeptidase A mRNAs decreased by greater than 50% during the acute phase (days 0-2), whereas actin and lithostathine mRNAs increased 5 and 0.6 times, respectively, and pancreatitis-associated protein (PAP) mRNA increased greater than 200 times, indicating redirection of the pattern of gene expression. Synthesis of pancreatic proteins was also altered in a noncoordinated manner. During the acute phase, it decreased more for trypsinogen I and chymotrypsinogen B than for amylase and lipase, whereas synthesis of the PAP increased dramatically. For amylase and chymotrypsinogen B, we compared the patterns of changes in mRNA concentrations, rates of synthesis, and pancreatic contents. Changes in enzyme contents and synthetic rates were temporally correlated during the acute phase. On the contrary, changes in mRNA concentrations and enzyme synthesis were not coordinated, suggesting that control of synthesis partly occurred at the posttranscriptional level. It was concluded that induction of pancreatitis is accompanied by transcriptional and posttranscriptional modifications resulting in rapid and massive rearrangement of the pattern of pancreatic protein gene expression.
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PMID:Pancreatic gene expression is altered during acute experimental pancreatitis in the rat. 171 58

Rat pancreatitis-associated protein (PAP) is an additional protein appearing in pancreatic juice after induction of prancreatic inflammation. Its messenger RNA was cloned and sequenced from pancreas. The deduced amino acid sequence revealed that PAP was synthetized as a preprotein with, in its mature form, a predicted molecular weight of 16,630. A search in protein data bases revealed a marked homology with the carbohydrate binding region of animal lectins; no hemagglutination activity could be shown for PAP, but the protein induced extensive bacterial aggregation. In healthy rats, the very low level of PAP expression in pancreas could be increased up to 4-fold by physiological stimuli such as chronic hormonal or cholinergic stimulation of pancreatic secretion and adaptation of rats to a carbohydrate-rich diet. By contrast, induction of acute experimental pancreatitis by retrograde injection of sodium taurocholate resulted in dramatic overexpression. Pancreatic concentration of PAP mRNA increased more than 300 x within 12 h whereas concentrations of mRNAs encoding major secretory proteins such as amylase decreased. PAP overexpression persisted during the 2 days of the acute phase and then returned to the control level during pancreatic recovery. PAP mRNA could not be evidenced in liver, stomach, salivary glands, brain, kidney, or testis. Its pattern of expression during severe pancreatic aggression suggests that it might be a stress protein involved in the control of bacterial proliferation.
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PMID:Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis. 172 11

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

An additional protein in rat pancreatic juice has been observed, which is present in healthy rats after pancreatic duct cannulation or in rats in which experimental pancreatitis has been induced by either cerulein or taurocholate. The protein appears 1/2-1 day after surgery or onset of pancreatitis, is present for the following 3-4 days and disappears afterwards. It is found in pancreatic homogenate or in zymogen granules from rats with pancreatitis, but not in normal rats. It does not seem to be related to the recently described 'pancreatic stone protein'. We would like to refer to this protein as 'pancreatitis-associated protein'.
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PMID:An additional secretory protein in the rat pancreas. 646 71

Expression of the pancreatitis-associated protein I (PAP I), an exocrine pancreatic protein, increases rapidly and strongly in acinar cells during the acute phase of pancreatitis. This is reminiscent of the response to stress of acute phase proteins. We have previously demonstrated that serum factors from rats with acute pancreatitis, but not from healthy rats, could induce endogenous PAP I gene expression in the acinar cell line AR-42J (Dusetti, N., Mallo, G., Dagorn, J.-C., Iovanna, J. L. (1994) Biochem. Biophys. Res. Commun. 204, 238-243). In the present work, we have evaluated the influence of several mediators of inflammation on rat PAP I gene transcription in these cells. Tumor necrosis factor alpha induced an increase in PAP I mRNA expression, and interferon gamma caused an even greater increase in PAP I mRNA level. These stimulations were antagonized by dexamethasone. Interleukin (IL)-1, IL-6, or dexamethasone alone were ineffective. Combinations of IL-1 with IL-6 or dexamethasone were also ineffective. IL-6 and dexamethasone together induced a marked stimulation of PAP I gene transcription, and this effect was slightly attenuated by IL-1. To analyze the cis-regulatory elements responsible for the induction of transcription, we fused a 1.2-kilobase segment of the rat PAP I promoter to the chloramphenicol acetyltransferase (CAT) gene as reporter. The resultant chimeric DNA was transfected into AR-42J cells. Addition of IL-6 or dexamethasone was ineffective, whereas their mixture increased the CAT activity 12 times. Progressive deletions of the PAP I promoter were then fused to the CAT gene, and the constructs were transfected to AR-42J cells. A 12-fold increase in CAT activity was seen upon IL-6/dexamethasone treatment with constructs containing more than 274 base pairs upstream from the cap site. In that region, two sequences are similar to the canonical IL-6 response element. Site-directed mutagenesis of these regions strongly decreased induction, showing that they were functional. PAP I should therefore be classified among acute phase proteins of class 2, whose expression is increased by IL-6 acting in combination with glucocorticoids.
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PMID:Pancreatitis-associated protein I (PAP I), an acute phase protein induced by cytokines. Identification of two functional interleukin-6 response elements in the rat PAP I promoter region. 754 77

To study the relation between expression of the pancreatitis-associated protein (PAP) and severity of pancreatitis in rats, different degrees of experimental pancreatitis were induced by a 1-, 3-, or 5-h cerulein infusion (5 micrograms kg-1 h-1). This treatment decreased pancreatic volume secretion to below 10%. Immediately after infusion, the secretion rate increased to approximately 50% of control. Within 1 day, volume and bicarbonate secretion rates were not different from controls. At this point, protein secretion amounted to 30% of control, but only in animals receiving the 3- or 5-h dose. The values increased to 40-60% within 3 days. In all groups, the isoenzyme pattern was not influenced by the cerulein treatment. One day after induction of pancreatitis, the PAP was found in pancreatic juice in concentrations related to the dose of cerulein given. By immunohistochemical techniques, the protein was localized over acinar cells, but was not detectable in interstitial tissue, islets, or in the healthy exocrine pancreas. Pathomorphologic alterations in the pancreas were quantified by a scoring system. One and 2 days after the treatment, a more severe pancreatitis and more elevated levels of PAP were found in animals treated with the higher dose of cerulein. It is concluded that PAP is expressed in the pancreas in relation to the severity of cerulein-induced pancreatitis.
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PMID:Rat pancreatitis-associated protein is expressed in relation to severity of experimental pancreatitis. 780 15

The pancreatitis-associated protein (PAP) is a lectin-related secretory protein present in small amounts in the rat pancreas and rapidly overexpressed during the acute phase of pancreatitis. We demonstrate in this report that PAP is also expressed in rat intestine. A cDNA library from rat jejunum was probed with pancreatic PAP cDNA. The inserts of the selected recombinant clones corresponded to a transcript whose nucleotide sequence was identical to that of pancreatic PAP mRNA. The transcript was detected in duodenum, jejunum, ileum, and colon. A protein with same molecular mass (16 kDa) and pI (8.2) as pancreatic PAP was actually immunodetected in ileum homogenate after separation by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Intestinal PAP was immunolocalized to the epithelial cells of the lower part of the villi. The protein accounted respectively for 0.02, 0.05, and 0.1% of soluble proteins in duodenum, jejunum, and ileum homogenates, as measured by enzyme-linked immunosorbent assay, and could not be detected in stomach and colon. Influence of fasting and feeding on PAP mRNA concentration was analyzed in ileum. Concentration decreased by 81 and 94% after animals were fasted for 24 and 48 h, respectively. Feeding restored the initial content within 6 h. On the other hand, intestinal PAP mRNA concentration was not altered during acute pancreatitis.
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PMID:PAP, a pancreatic secretory protein induced during acute pancreatitis, is expressed in rat intestine. 823 45

Rat pancreatitis-associated protein (PAP) mRNA is barely detectable in normal pancreas and overexpressed during acute pancreatitis (Iovanna, J., Orelle, B., Keim, V., and Dagorn J.-C. (1991) J. Biol. Chem. 266, 24664-24669). RNA amplification by reverse-transcriptase-coupled polymerase chain reaction showed that PAP mRNA was constitutively expressed in duodenum, jejunum, and ileum, at similar levels as in pancreas during the acute phase of pancreatitis. A weak expression was also detected in several other tissues. The rat PAP gene was isolated from a genomic library and characterized over 3.2 kilobases of gene sequence and 1.2 kilobases of 5'-flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP transcript. Several potential regulatory elements were identified in the promoter region, including a pancreas-specific consensus sequence, two Pan1 (pancreas-specific) transcription activators, two IL-6 response elements, and one glucocorticoid response element. The PAP coding sequence spanned over six exons. The first three exons encoded the 5'-untranslated region of the mRNA, the signal peptide, and 39 amino acids of the NH2-terminal end of the mature protein, respectively. The other three exons encoded a domain of the protein with significant homology to the carbohydrate-recognition domain of animal lectins. Sequence comparison of the PAP gene with 13 carbohydrate-recognition domain-containing genes revealed that they derived from the same ancestor gene. Position of introns within the carbohydrate-recognition domain were different, however, suggesting that PAP belongs to a new group of lectins. These results support the hypothesis that genes encoding PAP and other lectins evolved from a common ancestor gene by intron gain.
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PMID:Structural organization of the gene encoding the rat pancreatitis-associated protein. Analysis of its evolutionary history reveals an ancient divergence from the other carbohydrate-recognition domain-containing genes. 831 3


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