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PubMed1979

The two human trypsinogens. Evidence of complex formation with basic pancreatic trypsin inhibitor-proteolytic activity.

The formation of complexes between human trypsinogens and the basic pancreatic trypsin inhibitor is demonstrated by using affinity chromatography on Sepharose coupled to basic pancreatic trypsin inhibitor. This interaction indicates the pre-existence of the active site in human trypsinogens. This active site induces the proteolytic activity of the two zymogens which activate spontaneously at pH 5.6 and pH 8.0 before and after affinity chromatography. The effect of affinity-chromatography on trypsinogen spontaneous activation is not the same on trypsinogens 1 and 2. A striking difference appears between the activation of the two trypsinogens. In all cases, trypsinogen 1 autoactivates more rapidly than trypsinogen 2, except at pH 5.6 in the presence of 10 mM Ca2+, which inhibits the autoactivation of trypsinogen 1. The effect of inherent proteolytic activity of human trypsinogens is discussed in relation to pathological conditions of enterokinase deficiency and acute pancreatitis.

Calcium↗
PubMed2000

Expression and characterization of trypsinogen produced in the human male genital tract.

Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.

Blotting, Northern↗
PubMed1986

Abnormalities of circulating immunoreactive pancreatic anionic trypsinogen in cystic fibrosis: an assay artifact due to cross-reacting serum antibodies.

In patients with CF, serum pancreatic cationic trypsinogen has proven to be useful for newborn diagnostic screening and also as a test of pancreatic function in the older patient. However, an assay for serum anionic trypsinogen is of no value as a test of pancreatic function in CF due to an apparent artifactual elevation of this enzyme in some patients. In this study, we evaluated the extent of the abnormality in the anionic trypsinogen assay and also elucidated the nature of the interfering material. CF patients were grouped according to the presence (pancreatic insufficiency) or absence (pancreatic sufficiency) of steatorrhea. In CF infants, both serum cationic and anionic trypsinogen levels were greatly elevated. Serum cationic trypsinogen declined with age in patients with pancreatic insufficiency, reaching low or undetectable levels after 6 years. In contrast, serum anionic trypsinogen levels remained normal or elevated in 33% of those over 6 years of age. There was no age-related change in either cationic or anionic trypsinogen among the CF patients with pancreatic sufficiency, and the majority had normal or elevated levels. Serum samples from selected CF patients were separated into IgG and non-IgG fractions using Staph. Protein A columns. Immunoreactive cationic and anionic trypsinogen were detectable in the non-IgG fractions of sera from CF infants and older patients with pancreatic sufficiency. In older CF patients with undetectable serum cationic and anionic trypsinogen, no immunoreactive material was detectable in either the IgG or non-IgG fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Isolation and characterization of a cDNA encoding rat cationic trypsinogen.

A cDNA encoding rat cationic trypsinogen has been isolated by immunoscreening from a rat pancreas cDNA library. The protein encoded by this cDNA is highly basic and contains all of the structural features observed in trypsinogens. The amino acid sequence of rat cationic trypsinogen is 75% and 77% homologous to the two anionic rat trypsinogens. The homology of rat cationic trypsinogen to these anionic trypsinogens is lower than its homology to other mammalian cationic trypsinogens, suggesting that anionic and cationic trypsins probably diverged prior to the divergence of rodents and ungulates. The most unusual feature of this trypsinogen is the presence of an activation peptide containing five aspartic acid residues, in contrast to all other reported trypsinogen activation peptides which contain four acidic amino acid residues. Comparisons of cationic and anionic trypsins reveal that the majority of the charge changes occur in the C-terminal portion of the protein, which forms the substrate binding site. Several regions of conserved charge differences between cationic and anionic trypsins have been identified in this region, which may influence the rate of hydrolysis of protein substrates.

Amino Acid Sequence↗
PubMed1999

Blood immunoreactive trypsinogen concentrations are genetically determined in healthy and cystic fibrosis newborns.

Newborns with cystic fibrosis (CF) have increased blood immunoreactive trypsinogen concentrations. When screening for CF in the newborn by immunoreactive trypsinogen measurement, an abnormally high proportion of healthy deltaF508 carriers is found among false-positive neonates, suggesting that a relationship could exist between immunoreactive trypsinogen concentration at birth and the genetic status. Therefore, this study analysed the possible relationships between neonatal blood immunoreactive trypsinogen concentrations and genotype in 1842 healthy newborns and 111 CF patients detected by a neonatal screening programme. A close correlation was found between immunoreactive trypsinogen and deltaF508: the probability of a healthy newborn being a carrier of this mutation increased regularly with the neonatal immunoreactive trypsinogen concentration. In CF patients, there was a significant difference between deltaF508 homozygotes and deltaF508/X (X = other mutation) compound heterozygotes with respect to the mean neonatal blood immunoreactive trypsinogen concentration. CF neonates with two mutations affecting the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator protein had significantly higher mean immunoreactive trypsinogen concentrations than patients with one mutation affecting a membrane-spanning domain. The data strongly suggest that the neonatal immunoreactive trypsinogen concentration is, in part, genetically determined, with a wide range of variations, similar to the features which have been shown for the relations between the genotype and clinical phenotypes of CF patients.

Case-Control Studies↗
PubMed2003

Evolution of trypsinogen activation peptides.

The activation peptide of mammalian trypsinogens contains a highly conserved tetra-aspartate sequence (D19-D20-D21-D22) preceding the K23-I24 scissile peptide bond, which is hydrolyzed as the first step in the activation process. Here, we examined the evolution and function of trypsinogen activation peptides through integrating functional characterization of disease-associated mutations with comparative genomic analysis. Activation properties of three chronic pancreatitis-associated activation peptide mutants (the novel D19A and the previously reported D22G and K23R) were simultaneously analyzed, for the first time, in the context of recombinant human cationic trypsinogen. A dramatic increase in autoactivation of cationic trypsinogen was observed in all three mutants, with D22G and K23R exhibiting the most marked increases. The physiological activator enteropeptidase activated the D19A mutant normally, activated the D22G mutant very poorly, and stimulated activation of the K23R mutant. The biochemical and structural data, taken together with a comprehensive sequence comparison, indicates that the tetra-aspartate sequence in mammalian trypsinogen activation peptides has evolved not only for optimal enteropeptidase recognition in the duodenum but also for efficient inhibition of trypsinogen autoactivation within the pancreas. Moreover, the use of lysine instead of arginine at the P1 position of activation peptides also has an advantageous effect against trypsinogen autoactivation. Finally, fixed substitutions in the key residues of the trypsinogen activation peptide may suggest the evolution of new functions unrelated to digestion, as found in the group III trypsinogens of cold-adapted fishes.

Amino Acid Sequence↗
PubMed1981

The fate of intravenously injected trypsinogens in dogs.

After intravenous injection of autologous purified and radiolabeled anionic and cationic trypsinogens in the dog, there is a multiexponential elimination from serum of the trypsinogens without activation to active trypsins. The results are in agreement with an elimination of the trypsinogens iva glomerular filtration, a variable tubular uptake of anionic trypsinogen, and a complete tubular uptake of cationic trypsinogen. Fractional catabolic rates for anionic trypsinogen were 0.35-0.92 h-1 and for cationic trypsinogen 0.38-1.05 h-1. The total amount of anionic trypsinogen turned over in the circulation is estimated at approximately 0.55 mg every 24 h, and the corresponding figure for cationic trypsinogen is 0.35 mg/24 h.

Animals↗
PubMed2004

[Usefulness of urinary trypsinogen-2 dipstick test for diagnosis of acute pancreatitis].

BACKGROUND/AIMS: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis. METHODS: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls. RESULTS: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p=0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992. CONCLUSIONS: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.

Acute Disease↗
PubMed1982

Two similar but nonallelic rat pancreatic trypsinogens. Nucleotide sequences of the cloned cDNAs.

We have cloned and identified mRNA sequences for two rat pancreatic trypsinogens. Nucleotide sequence analysis of the cloned sequences revealed two mRNAs that encode similar, though noallelic, pretrypsinogens. Trypsinogen I mRNA is 804 nucleotides in length, plus an estimated poly(A) tract of 100 nucleotides, and contains a short (13 nucleotide) 5' noncoding region and a 3' noncoding region of 54 nucleotides. It encodes a preproenzyme of 246 amino acids comprising a hydrophobic prepeptide (signal peptide) of 15 amino acids, an activation peptide characteristic of trypsinogens, and an active form of trypsin, 223 amino acids in length, that has 78% amino acid sequence identity with porcine trypsin. Trypsinogen II mRNA has a nucleotide sequence 88% homologous with that of trypsinogen I mRNA and encodes a protein with 89% amino acid sequence identity with trypsinogen I. The enzymes encoded by trypsinogen I and II mRNAs retain the key amino acid residues that determine the characteristic substrate cleavage preference of trypsins and, therefore, represent the rat counterparts of this digestive enzyme. Trypsinogen I mRNA is a major pancreatic mRNA comprising an estimated 2-5% of the total, whereas trypsinogen II mRNA is present at much lower levels.

Alleles↗
PubMed2001

Enhanced invasiveness of pancreatic adenocarcinoma cells stably transfected with cationic trypsinogen cDNA.

Various studies have described increased expression of cationic trypsinogen in malignant tumor cells. To explore the role of secreted cationic trypsinogen in invasion by cancer cells, we introduced cationic trypsinogen cDNA into Panc-1, a pancreatic adenocarcinoma-derived cell line that lacks expression of endogeneous trypsinogen. Four independent clones (designated Panc-1-Try-7, -9, -11 and -24) stably expressing cationic trypsinogen mRNA were isolated and processed for further study. In a zymographic analysis, gelatinolytic activity for cationic trypsinogen was detectable in serum-free conditioned media obtained from all 4 transfectants but not in media from mock-transfected or parental Panc-1 cells. A Matrigel invasion assay revealed that all trypsinogen-expressing transfectants acquired significantly greater invasive ability than that shown by mock-transfected and parental Panc-1 cells. In addition, enhanced invasiveness of the transfectants was suppressed by FUT-175, a serine protease inhibitor, to the level seen in parental cells. These results provide direct evidence that cationic trypsinogen can increase the invasive ability of carcinoma cells.

Adenocarcinoma↗
PubMed2002

Spray-freeze-drying for protein powder preparation: particle characterization and a case study with trypsinogen stability.

This work investigates the use of spray freeze-drying (SFD) to produce protein loaded particles suitable for epidermal delivery. In the first part of the study, the effects of formulation and process conditions on particle properties are examined. Aqueous solutions of trehalose produce SFD particles in the size range 20-80 microm, with a smooth, textured surface, but having high internal porosity. The latter was visualized using SEM and a novel particle embedding and sectioning technique. Use of an annealing step during the freeze-drying cycle caused the particles to shrink, reducing hereby porosity and also the measured rate of moisture uptake into these amorphous particles. SFD pure mannitol was approximately 40% amorphous, but not hygroscopic. Incorporation of dextran 37,500 into a combined amorphous trehalose/mannitol formulation led to increased particle shrinkage and lower particle porosity on annealing. The model protein trypsinogen lost approximately 15% activity during SFD of solutions containing 50 mg/mL protein, but was only marginally aggregated (1.4%). It is suggested that trypsinogen forms an irreversible partially unfolded state or molten globule on SFD/rehydration. The pure protein was also partially inactivated without aggregation during atomization into air. Surprisingly, neither activity loss nor aggregation were detected on atomization of the protein solution into liquid nitrogen. Quench-freezing of small droplets may reverse the partial unfolding of trypsinogen occurring on atomization into air. The origin of the trypsinogen inactivation during SFD must therefore be the subsequent freeze-drying step of this multistep process. Isolated freeze drying of trypsinogen produces strong aggregation and equivalent inactivation. This result suggests that trypsinogen behaves differently during freeze drying from frozen droplets and from bulk solution in a vial. In the former case the protein forms an irreversible partially unfolded state, whereas in the latter case aggregates are formed. Trypsinogen inactivation during SFD could be completely prevented by the presence of trehalose in the formulation. Electron Spectroscopy for Chemical Analysis (ESCA) showed a high surface excess of the protein in the SFD particles, which was reduced on inclusion of Polysorbate 80, but not trehalose. Taken together, these results help to elucidate the complex destabilization behavior of trypsinogen during SFD.

Chromatography, Gel↗
PubMed1977

Structure of bovine trypsinogen at 1.9 A resolution.

The three-dimensional crystal structure of bovine trypsinogen at approximately pH 7.5 was initially solved at 2.6 A resolution using the multiple isomorphous replacement method. Preliminary refinement cycles of the atomic coordinates trypsinogen have been carried out first to a resolution of 2.1 A, and later to 1.9 A, using constrained difference Fourier refinement; During the process, structure factors Fc and phi c were calculated from the trypsinogen structure and final interpretation was based on an electron-density map computed with terms (2 Fo - Fc) and phases phic at a resolution of 1.9 A. Crystals of trypsinogen grown from ethanol-water mixtures are trigonal with space group P3121, and cell dimension a = 55.17 A and c = 109.25 A. The structure is compared with the bovine diisopropylphosphoryltrypsin structure at approximately pH 7.2, oirginally determined from orthohombic crystals by Stroud et al. (Stroud, R.M., Kay L.M., and Dickerson, R.E. (1971), Cold Spring Harbor Symp. Quant. Biol. 36, 125-140; Stroud, R.M., Kay, L.M., and Dickerson, R.E. (1974), J. Mol. Biol. 83, 185-208), and later refined at 1.5 A resolution by Chambers and Stroud (Chambers, J.L., and Stroud, R.M. (1976), Acta Crystallogr. (in press)). At lower pH, 4.0-5.5 diogen, with cell dimensions a = 55.05 A and c = 109.45 A. This finding was used in the solution of the six trypsinogen heavy-atom derivatives prior to isomorphous phase analysis, and as a further basis of comparison between trypsinogen and the low pH trypsin structure. There are small differences between the two diisopropylphosphoryltrypsin structures. Bovine trypsinogen has a large and accessible cavity at the site where the native enzyme binds specific side chains of a substrate. The conformation and stability of the binding site differ from that found in trypsin at approximately pH 7.5, and from that in the low pH form of diisopropylphosphoryltrypsin. The catalytic site containing Asp-102, His-57, and Ser-195 is similar to that found in trypsin and contains a similar hydrogen-bounded network. The carboxyl group of Asp-194, which is salt bridged to the amino terminal of Ile-16 in native trypsin or other serine proteases, is apparently hydrogen bonded to internal solvent molecules in a loosely organized part of the zymogen structure. The unusually charged N-terminal hexapeptide of trypsinogen, whose removal leads to activation of the zymogen, lies on the outside surface of the molecule. There are significant structural changes which accompany activation in neighboring regions, which include residues 142-152, 215-550, 188A-195. The NH group of Gly-193, normally involved in stabilization of reaction intermediates (Steitz, T.A., Henderson, R., and Blow, D.M. (1969), J. Mol. Biol. 46, 337-348; Henderson, R. (1970), J. Mol. Biol. 54, 341-354; robertus, J.D., Kraut, J., Alden, R.A., and Birkoft, J.J. (1972), Biochemistry 11, 4293-4303) in the enzyme, is moved 1.9 A away from its position in trypsin...

Animals↗
PubMed1995

Isolation and characterization of the chicken trypsinogen gene family.

Based on genomic Southern hybridizations and cDNA sequence analyses, the chicken trypsinogen gene family can be divided into two multi-member subfamilies, a six-member trypsinogen I subfamily which encodes the cationic trypsin isoenzymes and a three-member trypsinogen II subfamily which encodes the anionic trypsin isoenzymes. The chicken cDNA and genomic clones containing these two subfamilies were isolated and characterized by DNA sequence analysis. The results indicated that the chicken trypsinogen genes encoded a signal peptide of 15 to 16 amino acid residues, an activation peptide of 9 to 10 residues and a trypsin of 223 amino acid residues. The chicken trypsinogens contain all the common catalytic and structural features for trypsins, including the catalytic triad His, Asp and Ser and the six disulphide bonds. The trypsinogen I and II subfamilies share approximately 70% sequence identity at the nucleotide and amino acid level. The sequence comparison among chicken trypsinogen subfamily members and trypsin sequences from other species suggested that the chicken trypsinogen genes may have evolved in coincidental or concerted fashion.

Amino Acid Sequence↗
PubMed2002

Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis.

The lysosomal cysteine protease cathepsin B is thought to play a central role in intrapancreatic trypsinogen activation and the onset of experimental pancreatitis. Recent in vitro studies have suggested that this mechanism might be of pathophysiological relevance in hereditary pancreatitis, a human inborn disorder associated with mutations in the cationic trypsinogen gene. In the present study evidence is presented that cathepsin B is abundantly present in the secretory compartment of the human exocrine pancreas, as judged by immunogold electron microscopy. Moreover, pro-cathepsin B and mature cathepsin B are both secreted together with trypsinogen and active trypsin into the pancreatic juice of patients with sporadic pancreatitis or hereditary pancreatitis. Finally, cathepsin B- catalyzed activation of recombinant human cationic trypsinogen with hereditary pancreatitis-associated mutations N29I, N29T, or R122H were characterized. In contrast to a previous report, cathepsin B-mediated activation of wild type and all three mutant trypsinogen forms was essentially identical under a wide range of experimental conditions. These observations confirm the presence of active cathepsin B in the human pancreatic secretory pathway and are consistent with the notion that cathepsin B-mediated trypsinogen activation might play a pathogenic role in human pancreatitis. On the other hand, the results clearly demonstrate that hereditary pancreatitis-associated mutations do not lead to increased or decreased trypsinogen activation by cathepsin B. Therefore, mutation-dependent alterations in cathepsin B-induced trypsinogen activation are not the cause of hereditary pancreatitis.

Blotting, Western↗
PubMed2006

Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen.

Trypsin-mediated trypsinogen activation (autoactivation) facilitates digestive zymogen activation in the duodenum but may precipitate pancreatitis if it occurs prematurely in the pancreas. Autoactivation of human cationic trypsinogen is inhibited by a repulsive electrostatic interaction between the unique Asp218 on the surface of cationic trypsin and the conserved tetra-aspartate (Asp19-22) motif in the trypsinogen activation peptide (Nemoda, Z., and Sahin-Tóth, M. (2005) J. Biol. Chem. 280, 29645-29652). Here we describe that this interaction is regulated by chymotrypsin C (caldecrin), which can specifically cleave the Phe18-Asp19 peptide bond in the trypsinogen activation peptide and remove the N-terminal tripeptide. In contrast, chymotrypsin B, elastase 2A, or elastase 3A (proteinase E) are ineffective. Autoactivation of N-terminally truncated cationic trypsinogen is stimulated approximately 3-fold, and this effect is dependent on the presence of Asp218. Because chymotrypsinogen C is activated by trypsin, and chymotrypsin C stimulates trypsinogen activation, these reactions establish a positive feedback mechanism in the digestive enzyme cascade of humans. Furthermore, inappropriate activation of chymotrypsinogen C in the pancreas may contribute to the development of pancreatitis. Consistent with this notion, the pancreatitis-associated mutation A16V in cationic trypsinogen increases the rate of chymotrypsin C-mediated processing of the activation peptide 4-fold and causes accelerated trypsinogen activation in vitro.

Cations↗
PubMed2006

Human cationic trypsinogen is sulfated on Tyr154.

The crystal structure of human pancreatic cationic trypsin showed the chemical modification of Tyr154, which was originally described as phosphorylation [Gaboriaud C, Serre L, Guy-Crotte O, Forest E & Fontecilla-Camps JC (1996) J Mol Biol259, 995-1010]. Here we report that Tyr154 is sulfated, not phosphorylated. Cationic and anionic trypsinogens were purified from human pancreatic juice and subjected to alkaline hydrolysis. Modified tyrosine amino acids were separated on a Dowex cation-exchange column and analyzed by thin layer chromatography. Both human cationic and anionic trypsinogens contained tyrosine sulfate, but no tyrosine phosphate, whereas bovine trypsinogen contained neither. Furthermore, incorporation of [(35)S]SO(4) into human cationic trypsinogen transiently expressed by human embryonic kidney 239T cells was demonstrated. Mutation of Tyr154 to Phe abolished radioactive sulfate incorporation, confirming that Tyr154 is the site of sulfation in cationic trypsinogen. Sulfated pancreatic cationic trypsinogen exhibited faster autoactivation than a nonsulfated recombinant form, suggesting that tyrosine sulfation of trypsinogens might enhance intestinal digestive zymogen activation in humans. Finally, sequence alignment revealed that the sulfation motif is only conserved in primate trypsinogens, suggesting that typsinogen sulfation is absent in other vertebrates.

Animals↗
PubMed1997

Increased serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy.

AIMS: To evaluate the clinical utility of two new tests for serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex (trypsin 2-AAT) in diagnosing and assessing the severity of acute pancreatitis (AP) induced by endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS: Three hundred and eight consecutive patients undergoing ERCP at Helsinki University Central Hospital in 1994 and 1995. METHODS: Patients were followed prospectively for pancreatitis and clinical outcome. They were tested for serum trypsinogen 2, trypsin 2-AAT, and amylase in samples obtained before and one, six, and 24 hours after ERCP. RESULTS: Pancreatitis developed in 31 patients (10%). Their median serum trypsinogen 2 increased 26-fold to 1401 micrograms/l at six hours after the procedure and trypsin 2-AAT showed an 11-fold increase to 88 micrograms/l at 24 hours. The increase in both markers was stronger in severe than in mild pancreatitis, and in patients without pancreatitis there was no significant increase. Baseline trypsinogen 2 and trypsin 2-AAT concentrations were elevated in 29% and 32% of patients, respectively. The diagnostic accuracy of a threefold elevation over the baseline value was therefore analysed. The sensitivity and specificity of these parameters in the diagnosis of post-ERCP pancreatitis was 93% and 91%, respectively, for serum trypsinogen 2 at six hours after the examination, and 93% and 90%, for trypsin 2-AAT at 24 hours. CONCLUSIONS: Serum trypsinogen 2 and trypsin 2-AAT reflect pancreatic injury after ERCP. High concentrations are associated with severe pancreatic damage. The delayed increase in trypsin 2-AAT compared with trypsinogen 2 appears to reflect the pathophysiology of AP. A greater than threefold increase in trypsinogen 2 six hours after ERCP is an accurate indicator of pancreatitis.

Acute Disease↗
PubMed1998

Pancreatic trypsinogen I expression during cell growth and differentiation of two human colon carcinoma cells.

Pancreatic trypsin has been found to induce tight junction or dome formation in some colon cancer cell lines (HT-29, Caco-2), and a tumor-associated trypsinogen, trypsinogen type II, has been isolated from another colon cancer cell line (COLO 205). We have tried to determine if trypsinogen is present and how its expression varies during cell culture in HT-29 Glc+/- and Caco-2 cells, which exhibit enterocytic differentiation, and in HT-29 Glc+ cells, which never differentiate. Trypsinogen mRNA presence and expression were demonstrated in these cells by mRNA hybridization, RT-PCR, cytoimmunofluorescence, Western immunoblot analysis, and gel filtration. Trypsinogen was found to be trypsinogen type I and was mainly in zymogen form in culture media. Differentiating cells exhibited variations in trypsinogen I expression, but cells that remained undifferentiated did not. In the differentiated cells, a high and transient peak in trypsinogen I expression was observed during the first steps of differentiation.

Adenocarcinoma↗