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

Fusion genes combining the 5'-transcriptional regulatory region of the rat trypsin I gene and the structural gene of human growth hormone as a reporter were expressed to the high levels characteristic of the endogenous trypsin I gene selectively in the acinar cells of the pancreas of transgenic mice. As little as 232 base pairs of trypsin gene sequences containing the transcriptional start site and upstream promoter elements were sufficient to direct pancreatic expression. The tissue-specific expression was controlled transcriptionally. Trypsin-human growth hormone fusion transgenes also were expressed, although at low levels, in the stomach, an unexpected site for the expression of pancreatic digestive enzymes. Expression in the stomach of endogenous trypsin, elastase, and amylase genes in both normal and transgenic mice verified that transgene expression was consistent with normal expression of pancreatic genes. Endogenous amylase colocalizes with pepsinogen in the acinar cell-like Chief cells of the glandular portion of the mouse stomach. The expression of pancreatic genes in stomach cells is probably the consequence of similar developmental origins of pancreatic and gastric acinar cells from the primordial gut.
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PMID:Selective expression of trypsin fusion genes in acinar cells of the pancreas and stomach of transgenic mice. 146 18

Two major human pancreatic proteins, lipase and trypsin I, were measured in human sera from 35 elderly healthy adults and 51 young healthy adults. Lipase enzymatic activity was determined by a turbidimetric assay in the presence of colipase; lipase immunoreactive protein and trypsin immunoreactive protein were measured by using immunoenzymatic assays. Serum levels of the pancreatic enzymes were similar in young and elderly adults, with no significant differences between the groups for any of the assays. There was a close correlation between lipase enzyme activity and immunoreactivity in all participants, suggesting that the catalytic activity of lipase was not affected by aging. There were also significant correlations between the levels of immunoreactive lipase protein and immunoreactive trypsin protein, within and between the two groups, suggesting an age-independent relationship between these two pancreatic enzymes.
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PMID:Human serum pancreatic lipase and trypsin 1 in aging: enzymatic and immunoenzymatic assays. 355 2

A family of approximately 10 trypsin genes was detected in a rat genomic library by hybridization and in vivo recombination techniques using cloned rat pancreatic trypsin I and II cDNAs as probes. Two separate clones containing the entire trypsin I gene and most of the trypsin II gene were sequenced. Four introns split the trypsin I coding sequence. The positions of the first three introns of the trypsin II gene are identical with those in the trypsin I gene (the fourth intron was not present in the trypsin II clone). The coding regions of the two genes are 88% homologous; the 5'-noncoding regions are 92% homologous, whereas the 3'-noncoding regions share 66% identity. In contrast, the proximal 5'-flanking regions from -1 to -500 which may contain the elements controlling gene expression are less than 30% conserved overall, but segments of approximately 70% homology can be discerned in this region. Some of these sequences are homologous to sequences found in the chymotrypsin and elastase genes. More distal upstream sequences (-500 to -2500) and the intervening sequences show no evident sequence homology (less than 20%). Unique sequences containing homopolymeric purine/pyrimidine repeats are found 2.5 kilobases upstream from the start of transcription of the trypsin I gene and within the second and third introns of the trypsin II gene. The nucleotide homologies as well as the similarities of intron positions of the two trypsin genes to those of other serine protease genes clearly support an evolutionary relationship between members of this gene family.
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PMID:Structure of two related rat pancreatic trypsin genes. 609 47

The present work describes the effect of two soya bean protease inhibitors: Kunitz type (SBTI) and Bowman-Birk type (BBTI) on rat trypsin I (TrI), trypsin II (TrII) and chymotrypsin (Chtr) and on human cationic trypsin (hTr). The inhibition spectra show that: (1) SBTI inhibits TrI, TrII, Chtr and hTr esterase activities by 80, 80, 83 and 45%, respectively, at inhibitor-to-enzyme molar ratios of one-to-one, and (2) BBTI inhibits TrI, TrII, Chtr, and hTr esterase activities by 50, 65, 75 and 30%, respectively, at an inhibitor-to-enzyme molar ratio of two-to-one. A similar inhibition pattern was obtained by testing proteolytic activities. It would appear that hTr is less sensitive to soya bean protease inhibitors than each of the rat proteases investigated. This difference in inhibition should be considered when a rat is used as a model to predict the effects of dietary soya bean protease inhibitors on humans.
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PMID:Comparison of the interactions of soya bean protease inhibitors with rat pancreatic enzymes and human trypsin. 661 23

Increased secretion of matrix metalloproteinases and serine proteinases is well known to be associated with cancer invasion and metastasis. We aimed to elucidate the implication of trypsin, a serine proteinase and a representative digestive enzyme in invasion and metastasis of human carcinomas. Northern blot, RT-PCR and Western blot analyses and immunohistochemical studies were performed to detect and analyze trypsinogen expression in 5 ovarian carcinoma cell lines and 10 human ovarian carcinoma tissues using a DNA probe for trypsinogen I, and monoclonal and polyclonal antibodies to human trypsin I. Among the 5 ovarian carcinoma cell lines, only the MCAS (mucinous cystadenocarcinoma) cell line showed a high level of trypsinogen production and mRNA expression by Western and Northern blot analyses, respectively. However, Southern blot analysis of RT-PCR products could detect considerable levels of trypsinogen mRNA in all ovarian cancer cell lines. In Northern analysis of ovarian cancer tissues, all advanced cancer samples showed trypsinogen gene expression. Serous cystadenocarcinomas exhibited particularly high levels of gene expression. Immunohistochemical staining also detected trypsin in ovarian carcinoma tissues. In contrast, normal ovaries and tumors with low malignant potential did not show trypsinogen expression. Our results demonstrate the extra-pancreatic production and distribution of trypsinogen in human ovarian carcinomas.
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PMID:Trypsinogen expression in human ovarian carcinomas. 759 Dec

The stability of the mRNAs encoding pancreatic trypsin isozymes, namely the cationic form and the two anionic forms I and II, as well as that of the secretory trypsin inhibitors I and II, were studied in rats fed on either a high-protein diet, or a protein-free diet compared with a standard diet for a 10-day period. Either immediately or 3 h and 6 h after injecting the transcription inhibitor, actinomycin D, the mRNA levels were quantified by performing dot-blot hybridization with specific oligonucleotide probes. Under high-protein dietary conditions, the stability of the mRNAs coding for anionic trypsin II and cationic trypsin showed no change, whereas that of anionic trypsin I and the two forms of secretory trypsin inhibitor were affected. The mRNA half-life of anionic trypsin I and trypsin inhibitor II increased, in sharp contrast with that of trypsin inhibitor I, which decreased. When rats were fed on a protein-free diet, the stabilities of both anionic trypsin forms and trypsin inhibitor I increased, whereas that of trypsin inhibitor II decreased and that of cationic trypsin remained unchanged. The present results show the existence of differences in the mechanisms whereby gene expression of trypsin isozymes and secretory trypsin inhibitors is regulated, although they are synthesized in parallel in the pancreatic acinar cell and stored in zymogen granules before being secreted into the intestinal lumen.
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PMID:Dietary modulation of the mRNA stability of trypsin isozymes and the two forms of secretory trypsin inhibitor in the rat pancreas. 870 95

Four differently charged trypsins were purified from pyloric caeca of Atlantic salmon (Salmo salar). The isoelectric points of three anionic isoforms were 4.70, 4.60, and 4.55 (anionic trypsin I, II and III, respectively). And for the first time a cationic isoform (isoelectric point above 9.3) has been isolated from a marine species. The apparent molecular weights of all four isoforms were about 25 kDa as determined by SDS-PAGE. The salmon enzymes were inhibited by serine proteinase inhibitors in general and also by specific trypsin inhibitors. Anionic trypsin I and the cationic isoform were further examined. Anionic trypsin I showed the typical cold-adaptation features, low pH and temperature stability (also lower Gibb's free energy of GdnHCl-induced unfolding) and high catalytic efficiency as compared to the mammalian trypsins. The cationic isoform did not show these features, but resembled the mammalian trypsins.
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PMID:Temperature and pH sensitivity of trypsins from Atlantic salmon (Salmo salar) in comparison with bovine and porcine trypsin. 889 31

Severe neurodegradative brain diseases, like Alzheimer, are tightly linked with proteolytic activity in the human brain. Proteinases expressed in the brain, such as human trypsin IV, are likely to be involved in the pathomechanism of these diseases. The observation of amyloid formed in the brain of transgenic mice expressing human trypsin IV supports this hypothesis. Human trypsin IV is also resistant towards all studied naturally occurring polypeptide inhibitors. It has been postulated that the substitution of Gly193 to arginine is responsible for this inhibitor resistance. Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution. The overall fold of human trypsin IV is similar to human trypsin I, with a root-mean square deviation of only 0.5 A for all C(alpha) positions. The crystal structure reveals the orientation of the side-chain of Arg193, which occupies an extended conformation and fills the S2' subsite. An analysis of surface electrostatic potentials shows an unusually strong clustering of positive charges around the primary specificity pocket, to which the side-chain of Arg193 also contributes. These unique features of the crystal structure provide a structural basis for the enhanced inhibitor resistance, and enhanced substrate restriction, of human trypsin IV.
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PMID:Crystal structure reveals basis for the inhibitor resistance of human brain trypsin. 1182 88

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. In search of such target processing proteases in the airway, we recently found a new candidate trypsin-like processing protease in rat lungs, which was induced by Sendai virus infection, and identified as ectopic rat anionic trypsin I. On SDS/PAGE under reducing and nonreducing conditions, the purified enzyme gave protein bands corresponding to 29 and 22 kDa, respectively, i.e. at the same positions as rat pancreatic anionic trypsin I. It exhibited an apparent molecular mass of 31 kDa on molecular sieve chromatography and its isoelectric point was pH 4.7. The amino-acid sequences of the N-terminus and proteolytic digest peptides of the purified enzyme were consistent with those of rat pancreatic anionic trypsin I. Its substrate specificities and inhibitor sensitivities were the same as those of the pancreatic enzyme. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and hemagglutinin of human influenza A virus, and potentiated the infectivity of Sendai virus in the same dose-dependent manner as the pancreatic one. Immunohistochemical studies revealed that this protease is located in the stromal cells in peri-bronchiolar regions. These results suggest that ectopic anionic trypsin I in rat lungs induced by virus infection may trigger virus spread in rat lungs.
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PMID:Identification of ectopic anionic trypsin I in rat lungs potentiating pneumotropic virus infectivity and increased enzyme level after virus infection. 1202 1

PARs (protease-activated receptors) are a family of four G-protein-coupled receptors for proteases from the circulation, inflammatory cells and epithelial tissues. This report focuses on PAR(2), which plays an important role in inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by lysosomal targeting and degradation, which requires ubiquitination of PAR(2). beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling complexes that determine the location and function of activated mitogen-activated protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2) in inflammation, and many of the effects of PAR(2) activators promote inflammation. Inflammation is mediated in part by activation of PAR(2) in the peripheral nervous system, which results in neurogenic inflammation and hyperalgesia.
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PMID:Protease-activated receptor 2: activation, signalling and function. 1464 Oct 24


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