Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant plasmids coding for fusion proteins which consist of human adrenocorticotropin joined to N-terminal sequences of Escherichia coli alkaline phosphatase via collagenase-sensitive linkers were constructed and used for the production of these proteins by transformed E. coli cells. It was shown that repetitive linkers of the form -Gly-(Pro-Xaa-Gly)n-Pro- with n greater than or equal to 2 were cleaved by clostridiopeptidase A (Clostridium histolyticum) by orders of magnitude faster than corresponding nonrepetitive sequences (n = 1). The C-terminal cleavage product was Gly-Pro-adrenocorticotropin which could be converted to the authentic hormone by dipeptidyl peptidase IV. On the basis of these enzymatic reactions a procedure for the preparation of pure adrenocorticotropin was developed. Derivatives of alkaline phosphatase containing similar repetitive linker sequences were cleaved by clostridiopeptidase A as efficiently as the adrenocorticotropin fusion proteins.
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PMID:Production of human adrenocorticotropin by cleavage of alkaline-phosphatase-derived fusion proteins containing repetitive recognition sequences for collagenases. 257 29

The activities of collagenase-like peptidase, estimated by using (succinyl-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide as substrate, and of dipeptidyl-aminopeptidase IV were decreased in the sera from patients with rheumatoid arthritis. Both enzymes bring about the degradation of peptides derived from collagen. A significant positive correlation was observed between the activities of the two serum peptidases.
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PMID:Collagenase-like peptidase activity in serum from patients with rheumatoid arthritis. 285 19

The significance of glandular organization in exocrine secretion was examined by analysing the functional and morphological features of the dissociated rat submandibular gland with special reference to the acinar structure and luminal specialization. The digestion of the gland with collagenase (C preparation) produced relatively large cellular masses having well-preserved acinar structures. When EGTA and the proteolytic enzyme Dispase were added to the C preparation (CED preparation), the gland was dissociated into small cellular aggregates in which the acinar structure disintegrated. Upon stimulation with either isoproterenol or dibutyryl cyclic AMP, a large amount of peroxidase, one of the secretory products of the rat submandibular gland, was released from C-treated cells, while discharged peroxidase was greatly reduced after the CED preparation was used. Measurements of dye exclusion, oxygen consumption, protein synthetic activity and receptor binding, as well as ultrastructural features and the absence of inhibitory effects of EGTA and Dispase, suggested that the reduced secretory response of CED-treated cells was not attributable to cellular death, denaturation of receptors or the inhibitory effects of EGTA and Dispase. When the localization of dipeptidyl aminopeptidase IV was surveyed by both enzyme histochemistry and immuno-histochemistry, the luminal plasma membrane was the exclusive site for the reaction in C-treated cells as well as intact acini, whereas the entire cell surface was reaction-positive in CED-treated cells. In addition, the luminal microfilament system and tight junctions, as revealed by nitrobenz-oxadiazole-phallacidin staining and freeze-replica studies, respectively, were well-preserved in the C-treated cells, but considerably disorganized in the CED-treated cells. All these results strongly suggest that: (1) luminal specialization plays an important role in exocrine secretion; and (2) normal acinar arrangement provides the luminal specialization.
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PMID:Acinar structure and membrane regionalization as a prerequisite for exocrine secretion in the rat submandibular gland. 300 47

The early phase of wound healing after small central alkali burns of the guinea pig cornea was studied using electron microscopical, enzyme histochemical, and biochemical techniques. In the first phase, which was morphologically characterized by the destruction of the epithelium and keratocytes and by the infiltration of the cornea with polymorphonuclear leukocytes, an increase in the activity of lysosomal phosphatases and glycosidases (beta-D-glucuronidase, acid beta-D-galactosidase, beta-D-N-acetylglucosaminidase) was noticed. In the second phase, the cornea was invaded by capillaries and fibroblasts. In this phase, the activity of proteases (aminopeptidase M, dipeptidyl peptidase IV) increased intra- and extracellularly, suggesting that these enzymes may be involved in the turnover of the collagenous matrix and the ground substance. Using synthetic 4-methoxy-2-naphthylamine substrates and fluorescence-band detection techniques after isoelectric focusing, an increase in the activity of endopeptidases was demonstrated. The decreased activity of gamma-glutamyl transpeptidase may be linked with the activation of latent collagenase.
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PMID:The alkali burned cornea: electron microscopical, enzyme histochemical, and biochemical observations. 406 94

We report on the use of several proximal tubular cell (PTC) surface markets and corresponding antibodies in fluorescence-activated cell sorting (FACS), and their ability to identify and flow sort cells of defined proximal tubular origin (S1S2S3) or of defined proximal subsegmental origin (S1S2 only/S3 only). We tested monoclonal/polyclonal antibodies directed against five different surface peptidases [leucine aminopeptidase (LAP), neutral endopeptidase 24.11 (NEP), dipeptidyl peptidase IV (DPPIV), aminopeptidase A (APA) and gamma-glutamyl transferase (gamma-GT)], the S3 segment-specific marker intestinal type alkaline phosphatase (iAP) and an S1S2 marker (TN20-antigen), originally proposed as a surface marker for interstitial fibroblasts. Segmental (proximal tubular vs. distal tubular) and proximal subsegmental (S1S2 vs. S3) expression of all five surface peptidases and TN20 antigen were first assessed by comparing immunohistochemical staining on normal human kidney tissue with staining for well-known segment-specific differentiation markers (intestinal type alkaline phosphatase, Tamm-Horsfall protein) on adjacent sections. All five peptidases were found to be expressed to a certain degree in all subsegments (S1 S2 and S3) of the proximal nephron, whereas expression was never seen in the more distal parts of the nephron. Flow cytometry was performed on cells obtained following gradient purification of collagenase-digested human renal tissue. Labeling cells for expression of LAP, NEP or DPPIV resulted in high yields of specifically labeled PTC (S1S2S3 origin). Labeling with anti-LAP resulted in the clearest distinction between positive and negative cell subpopulations, and therefore LAP was considered the best PTC marker for use in FACS. iAP histochemical staining on sorted cells showed that flow sorting with monoclonal antibody (moAb) 250 (anti-intestinal type alkaline phosphatase) allowed sorting of S3 cells with > 90% purity. Likewise, moAb TN20 enabled us to obtain a highly purified S1S2 population as confirmed by the absence of iAP on sorted cells.
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PMID:Immunodissection of the human proximal nephron: flow sorting of S1S2S3, S1S2 and S3 proximal tubular cells. 926 97

An inhibitor of the metallo-ectoenzyme, pyroglutamyl aminopeptidase II (PPII), a thyrotropin releasing hormone-specific peptidase, was identified by screening extracts from marine species of the Cuban coast-line belonging to the phylla Chordata, Echinodermata, Annelida, Mollusca, Cnidaria, Porifera, Chlorophyta and Magnoliophyta. Isolation of the inhibitor (HcPI), from the marine annelide Hermodice carunculata, was achieved by trichloroacetic acid treatment of the aqueous extract, followed by ion-exchange chromatography on DEAE Sephacel, gel filtration on Sephadex G-25 and reverse phase-HPLC. HcPI had a small apparent molecular weight (below 1000 Da) and was not a peptide. It inhibited rat PPII (a membrane preparation with 8.5mg protein/ml) with an apparent K(i) of 51 nM. HcPI did not inhibit serine (trypsin, chymotrypsin, elastase and dipeptidyl aminopeptidase IV), cysteine (papain, bromelain and pyroglutamyl aminopeptidase I), aspartic (pepsin and recombinant human immunodeficiency virus 1 protease (HIV1-PR)) nor other metallo proteinases (collagenase, gelatinase, angiotensin converting enzyme, aminopeptidase N and carboxypeptidase A). HcPI was non-toxic and active in vivo. Intraperitoneal injection of HcPI reduced mouse pituitary and brain PPII activity. Potency of the effect was higher in hypophysis and hypothalamus than in other brain regions. Intrathecal administration to male rats reduced PPII activity in the spinal cord. In conclusion we have identified a specific inhibitor of PPII that is the first M1 family zinc metallo-peptidase inhibitor isolated from marine invertebrates. It may be useful for elucidating the in vivo role of PPII in the pituitary and central nervous system.
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PMID:Purification of a specific inhibitor of pyroglutamyl aminopeptidase II from the marine annelide Hermodice carunculata. in vivo effects in rodent brain. 1459 39

Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.
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PMID:Molecular mechanism for connective tissue destruction by dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis. 1584 67

Injury and repair in chronic liver disease involve cell adhesion, migration, apoptosis, proliferation, and a wound healing response. In liver, fibroblast activation protein (FAP) has both collagenase and dipeptidyl peptidase IV (DPIV) activities and is expressed only by activated hepatic stellate cells (HSC) and myofibroblasts, which produce and degrade extracellular matrix (ECM). FAP was colocalized with collagen fibers, fibronectin, and collagen type I in human liver. FAP function was examined in vitro by expressing green fluorescent protein FAP fusion protein in cell lines cultured on collagen-I, fibronectin, and Matrigel. Glutamates at 203 and 204 as well as serine624 of FAP were essential for peptidase activity. Human embryonic kidney 293T cells overexpressing FAP showed reduced adhesion and migration. FAP overexpression in the human HSC line LX-2 caused increased cell adhesion and migration on ECM proteins as well as invasion across transwells in the absence or presence of transforming growth factor beta-1. FAP overexpression enhanced staurosporine streptomyces-stimulated apoptosis in both cell lines. Interestingly, the enzyme activity of FAP was not required for these functions. Overexpressing FAP increased the expression of matrix metalloproteinase-2 and CD44 and reduced integrin-beta1 expression in 293T cells, suggesting potential pathways of FAP-mediated impairment of cell adhesion and migration in this epithelial cell line. In conclusion, these findings further support a pro-fibrogenic role for FAP by indicating that, in addition to its enzymatic functions, FAP has important nonenzymatic functions that in chronic liver injury may facilitate tissue remodeling through FAP-mediated enhancement of HSC cell adhesion, migration, and apoptosis.
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PMID:Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. 1617 1

The deep penetrating nevus is a rare variant of benign melanocytic nevus with histologic features mimicking vertical growth phase, nodular malignant melanoma. In this study, we expand on the search for new complementary discriminating markers by analyzing a selection of both cell cycle-related factors, such as retinoblastoma protein and phospho-retinoblastoma protein Ser795 as indicators for retinoblastoma protein activation/inactivation status, and invasion-related factors, such as matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3. MIB-1/Ki-67 was analyzed as an example for a common proliferation marker. Dipeptidyl peptidase IV/CD26 was analyzed as a marker affecting both proliferation and invasion of malignant melanocytic tumors. Semiquantitative assessment of both immunolocalization and immunoreactivity of retinoblastoma protein and phospho-retinoblastoma protein Ser795, MIB-1/Ki-67, matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3 revealed no consistent differences between deep penetrating nevi (n=14) and matched cases of nodular malignant melanomas (n=10). Matrix metalloproteinase-1 and matrix metalloproteinase-2 immunostaining of some deep penetrating nevi even exceeded that of nodular malignant melanomas. Membrane-type matrix metalloproteinase-1 expression scores of nodular malignant melanomas were higher than those of deep penetrating nevi, which was, however, not significantly discriminative. In contrast, immunostaining of dipeptidyl peptidase IV was significantly discriminative due to a consistent lack of dipeptidyl peptidase IV-expression in nodular malignant melanomas. These results add evidence that among the selected markers supposed to be relevant for melanoma progression the presence of dipeptidyl peptidase IV can be used to support diagnosis of deep penetrating nevi in doubtful cases. As loss of dipeptidyl peptidase IV may also be causally linked to the transition of invasive to metastatic phenotypes, the molecular mechanisms downstream of dipeptidyl peptidase IV deserve to be studied in more detail in future investigations.
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PMID:Loss of dipeptidyl peptidase IV immunostaining discriminates malignant melanomas from deep penetrating nevi. 1682 52

In the present report, we have compared the phenotype and growth of small hepatocyte progenitors (SHPs) induced by retrorsine/partial hepatectomy (R/PH) and small hepatocytes (SHs) isolated from normal adult liver. SHs were isolated by a combination of differential centrifugation and Percoll isodensity fractionation from a liver cell suspension prepared by collagenase perfusion of a dipeptidyl peptidase IV (DPPIV)-positive Fischer F344 rat liver. Following further purification by flow cytometry, the SH-R3 fraction was transplanted via the portal vein into R/PH-treated, DPPIV-negative Fischer F344 rats. Frozen sections from tissue harvested at 5, 7, and 21 days after transplantation were analyzed by indirect immunofluorescence to compare the phenotypic characteristics of colonies formed by exogenous SH-R3s and endogenous SHPs. Colonies of transplanted SHs and endogenous SHPs displayed similar histologies and phenotypes but were distinguished from surrounding hepatocytes by their elevated expression of transferrin receptor. SH-R3 colonies were frequently located within clusters of gamma-glutamyl transpeptidase-positive host hepatocytes. Although significantly smaller at 5 and 7 days after PH, by day 21, SH-R3 colonies were similar in size to those formed by SHPs. The present results suggest that endogenous SHPs are derived, at least in part, from SHPs.
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PMID:Endogenous and transplanted small hepatocytes in retrorsine-treated/partially hepatectomized rat liver show differences in growth, phenotype, and proximity to clusters of gamma-glutamyl transpeptidase-positive host hepatocytes. 1978 12


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