Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We wished to determine whether the stimulation of protein synthesis by CCK8, carbachol, and insulin in isolated rat pancreatic acini resulted from translational or transcriptional induction of protein synthesis, and whether these hormones had similar or different effects on the rates of synthesis of individual enzymes. Isolated pancreatic acini were prepared from streptozocin-treated rats by collagenase digestion, mechanical dissociation, and centrifugation through a bovine serum albumin (BSA) cushion. Sixty-minute incubations, with maximally effective doses of CCK8, carbachol, and insulin, produced a 50, 90, and 100% increase, respectively, in the rate of protein synthesis. After inhibition of transcription with actinomycin D, the hormones still produced a 23, 50, and 61% increase, respectively, in the rate of protein synthesis. The study of the effect of the three hormones and the combination of CCK8 and insulin on the rate of synthesis of trypsinogen, chymotrypsinogen, lipase, and amylase, purified by isoelectric focusing, demonstrated that the hormones induced similar effects on the pattern of enzyme synthesis, and that they all induced the rate of synthesis of chymotrypsinogen slightly more than that of the other enzymes studied. We conclude that the hormones studied exert similar posttranscriptional influences in the regulation of protein synthesis in the pancreatic acinar cell.
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PMID:Translational control of protein synthesis in isolated pancreatic acini: role of CCK8, carbachol, and insulin. 243 15

A beta 1-serum component, beta 1-anticollagenase, capable of inhibiting various mammalian tissue collagenases, was isolated from human plasma by gel filtration, affinity chromatography and ion-exchange chromatography. The inhibitor contains 1-2 free sulfhydryl groups, which are a prerequiste for inhibitory activity and for binding to the thiol-Sepharose affinity support. Alkylation of beta 1-anticollagenase by iodoacetamide blocks inhibitory activity. The inhibitor was purified to apparent homogeneity and exhibited a Mr = 30500 determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The amino acid and carbohydrate composition was determined. According to its composition and the isoelectric focussing beta 1-anticollagenase is an acidic protein with an isoelectric point of 5.6. Inhibition of human leukocyte collagenase proceeds in a strong 1 : 1 stoichiometric reaction. The mechanism of this association takes place by a disulfide/thiol interchange reaction as has been previously indicated for human leukocyte collagenases in forming the latent enzyme [Macartney, H. W. and Tschesche, H. (1980) FEBS Lett. 119, 327-332]. The beta 1-anticollagenase--leukocyte-collagenase complex (latent enzyme) is activatable by disulfide-containing compounds such as cystine, oxidised glutathione, insulin, relaxin, trypsinogen and others, but not by 179,203-di(S-carboxymethyl)trypsinogen, or its trypsin derivative. Compounds containing inaccessible disulfide bonds, e.g. chymotrypsin, or sulfhydryl groups, e.g. D-penicillamine, do not activate the complex. Activation is, however, easily obtained with the oxidised-glutathione-generating system myeloperoxidase/H2O2/glutathione as was previously demonstrated for the human leukocyte latent collagenase activatable in a phagocytosis-simulated respiratory burst [Tschesche, H. and Macartney, H. W. (1981) Eur. J. Biochem. 120, 183-190].
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PMID:Characterisation of beta 1-anticollagenase from human plasma and its reaction with polymorphonuclear leukocyte collagenase by disulfide/thiol interchange. 629 99

Primitive biliary cells are known to migrate from the ductal plate into the mesenchyme during human intrahepatic bile duct development, and this migration process is essential for normal development of intrahepatic bile ducts. However, its molecular mechanism is unknown. Matrix proteinases play an important role in cell migration during cancer invasion and organ development. In this study, we therefore investigated in situ expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) during human intrahepatic bile duct development, using 32 human fetal livers. We also examined in situ expression of trypsinogen/trypsin, chymotrypsinogen/chymotrypsin, and cathepsin B, which are matrix proteinases and activators of MMP. MMP-1 expression was noted in the ductal plate and migrating primitive biliary cells. MMP-2, MMP-3, and MMP-9 were expressed in the ductal plate. TIMP-1 and TIMP-2 were expressed in the ductal plate and migrating primitive biliary cells. Trypsinogen/trypsin, chymotrypsinogen/chymotrypsin, and cathepsin B were also expressed in primitive biliary cells. These data suggest that MMP, trypsinogen/trypsin, chymotrypsinogen/chymotrypsin, and cathepsin B play a critical role in biliary cell migration during human intrahepatic bile duct development by degrading extracellular matrix proteins. The data also suggest that MMP inhibitors (TIMP-1 and TIMP-2) and MMP activators (trypsin, chymotrypsin, and cathepsin B) play an important role in biliary cell migration. The coordinated expression of MMP, MMP inhibitors, and MMP activators may be necessary for the normal development of human intrahepatic bile ducts.
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PMID:Expression of matrix proteinases during human intrahepatic bile duct development. A possible role in biliary cell migration. 748 84

Morphology and immunohistochemical features of the developmental process of the human intrahepatic biliary system (IBS) are reviewed. Human IBS arises from the ductal plate, a double-layered cylindrical structure located at the interface between portal mesenchyme and primitive hepatocytes. The ductal plate first appears from primitive hepatocytes (hepatoblasts) around 8 gestational weeks (GW), and its formation proceeds from the hepatic hilum to the periphery. The ductal plate gradually undergoes remodeling from 12 GW; some parts of the ductal plate disappear and other parts migrate into the portal mesenchyme. Around 20 GW, the migrated duct cells transform into immature bile ducts and peribiliary glands. Some immature peribiliary glands transform into pancreatic acinar cells around postnatal 3 months. The immature biliary elements express cytokeratins no. 7, 8, 18 and 19. Several growth factors (TGF-alpha, HGF) and their receptors (EGFR, MET, ERBB2) were expressed in the primitive IBS cells. Some extracellular matrix proteins including type IV collagen, laminin and tenascin are expressed in the mesenchyme around the primitive IBS. During IBS remodeling, apoptosis and cell proliferation occur with appropriate expression of apoptosis-related proteins (bcl-2, Fas, c-myc, Lewis(y)). Some pancreatic digestive enzymes (alpha-amylase, trypsinogen, lipase), cathepsin B, and matrix metalloproteinases (MMP-1, 2, 3, 9) and their inhibitors (TIMP-1, 2) are expressed in the remodeling IBS cells. Glycoconjugate residues of glycoproteins gradually appear during IBS development. The appropriate expression of these immunophenotypes may play an important role in the normal development of IBS.
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PMID:Normal and abnormal development of the human intrahepatic biliary system: a review. 914 36

Proteolytic enzymes, such as matrix metalloproteinases (MMPs) and tumor-associated trypsinogens (TAT), play a pivotal role in tumor invasion and metastasis. Among MMPs, the interstitial collagenases (MMP-1, -8 and -13) can initiate collagenolysis. In this study, we have studied the levels of MMP-1, -8 and -13 in relation to the level of trypsinogen-2 in fluid from benign and malignant ovarian cysts. Elevated MMP-8 levels occur in many ovarian cyst fluids, and high MMP-8 levels are associated with malignancy. The concentrations of trypsinogen-2 correlate with those of MMP-8, but it remains to be shown whether trypsin-2 plays a role as its activator in vivo. The strong expression of MMP-8 over MMP-1 and MMP-13 in malignant ovarian tumors may indicate that MMP-8 participates in the protease cascades associated with the invasiveness of ovarian tumors.
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PMID:Collagenases (MMP-1, -8 and -13) and trypsinogen-2 in fluid from benign and malignant ovarian cysts. 1274 21