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)

We examined the activities of peptidases in the synovial membrane from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase II (DPP II), prolyl endopeptidase (PEP), and collagenase-like peptidase (CLP) activities were higher in knee joint synovial membrane from patients with RA than in that from patients with OA. DPP II and PEP activities in knee joint synovial membrane of patients with RA increased in parallel with the increase in joint fluid volume, whereas DPP IV activity decreased in parallel with the increase in joint fluid volume. These results suggest that these peptidases in the synovial membrane may play some role in immunological disturbances in the joints of patients with RA. Measurement of these peptidases in synovial membrane may be useful in the diagnosis of the severity of local joint inflammation.
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PMID:Activities of dipeptidyl peptidase II, dipeptidyl peptidase IV, prolyl endopeptidase, and collagenase-like peptidase in synovial membrane from patients with rheumatoid arthritis and osteoarthritis. 167 39

The activity of DPP II was higher in gingiva from patients with periodontitis, but the activity of DPP IV, post-proline cleaving enzyme and collagenase-like peptidase was not significantly higher than that of the control group. As DPP II activity is known to be altered in immunological diseases, these findings may suggest some role for DPP II in the pathogenesis of chronic marginal periodontitis.
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PMID:Activity of dipeptidyl peptidase II and dipeptidyl peptidase IV in human gingiva with chronic marginal periodontitis. 198 Aug 11

The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 micrograms/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.
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PMID:Effect of chlorpromazine on PZ-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1). 282 22

The effects of prostaglandin E2(PGE2) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells were investigated by using highly sensitive assay methods for PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP), and post-proline cleaving enzyme (PPCE). PGE2, at concentrations of 0.1 to 4.0 micrograms/ml, doubled the PZ-peptidase and CL-peptidase activities in the cells on 24 h culturing in a dose-dependent manner. PGE2, at a concentration of 2.0 micrograms/ml, enhanced the specific activities of PZ-peptidase, CL-peptidase, DAP, LAP, and PPCE for 75 h after the start of PGE2 stimulation. The time dependent changes in PZ-peptidase and CL-peptidase activities showed similar patterns, and 3- and 2-fold increases were seen after 48 h, respectively. The protein and DNA contents gradually increased after addition of PGE2. Since the PZ-peptidase and CL-peptidase, involved in degradation of collagen peptides, were significantly induced by PGE2 in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that PGE2 specifically stimulates induction of collagen catabolizing enzymes in clonal osteoblasts.
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PMID:Effect of prostaglandin E2 on PZ-peptidase and several other peptidase activities in a clonal osteoblast-like cell line derived from newborn mouse calvaria. 299 71

The histologic changes in the temporo mandibular joint (TMJ) and the activity of serum collagenase-like (CL) peptidase and prolyl endopeptidase (PEP) were compared in mice with spontaneous osteoarthrosis (C57 black mouse/6 Silverberg (C57BL/6S) and control mice (C57 black mouse/6N (C57BL/6N) and ddY). The onset of osteoarthrosis of the TMJ in the C57BL/6S mice was noted at 12 weeks of age. Clefting in the chondrocyte layer was noted at 24 to 36 weeks of age; chondrocyte cluster and pannus at 36 to 60 weeks of age; and clefts deep in the bone and formation of osteophytes at 72 to 96 weeks of age. CL-peptidase and PEP activity significantly higher in C57BL/6S mice than in osteoarthrosis-free C57BL/6N and ddY mice. These changes occurred at an earlier age than the histologic changes. The findings suggest that these enzymes may play a significant role in the onset of osteoarthrosis in joints.
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PMID:The relationship between collagen metabolism and temporomandibular joint osteoarthrosis in mice. 838 94

Protease activities with specificity toward synthetic substrates, Suc-Gly-Pro-Leu-Gly-Pro-MCA for prolyl endopeptidase or collagenase-like peptidase, and Suc-Ala-Ala-Pro-Phe-MCA for chymotrypsin were identified in the detergent-soluble fraction of herring spermatozoa. The enzyme activities increased in the presence of herring sperm-activating protein (HSAP). Among them a prolyl endopeptidase [EC. 3. 4. 21. 26] was purified to near homogeneity from herring testis. The molecular mass of the enzyme was 79 kDa and the properties of the enzyme were quite similar to prolyl endopeptidase from other tissues or cells. Both the enzyme activation and the sperm motility activation by HSAP were inhibited by benzyloxycarbonyl-L-thioproline-thioprolinal, a specific inhibitor for prolyl endopeptidase. Furthermore, the motility activation by HSAP was inhibited by substrates of the prolyl endopeptidase. Western blotting with mouse anti-prolyl endopeptidase serum revealed the presence of 79 kDa prolyl endopeptidase in the tail fraction of herring sperm. These results suggest that prolyl endopeptidase exists on the surface of the sperm tail and interacts with the HSAP.
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PMID:Purification and characterization of prolyl endopeptidase from the Pacific herring, Clupea pallasi, and its role in the activation of sperm motility. 1022 18

Human fibroblast activation protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein selectively expressed by fibroblastic cells in areas of active tissue remodeling, such as the embryonic mesenchyme, areas of wound healing, the gravid uterus, and the reactive stroma of epithelial cancers. Homologues of FAP have been identified in the mouse and Xenopus laevis. FAP is a dual-specificity enzyme that acts as a dipeptidyl peptidase and collagenase in vitro. To explore the role of FAP in vivo, Fap(-/-) mice were generated by homologous recombination. RNase protection analysis and reverse transcription-PCR confirmed the absence of full-length Fap transcripts in mouse embryonic tissues. No FAP protein was detected in Fap(-/-) animals by immunohistochemistry, and no FAP-specific dipeptidyl peptidase activity was found. We report that Fap(-/-) mice are fertile, show no overt developmental defects, and have no general change in cancer susceptibility.
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PMID:Targeted disruption of mouse fibroblast activation protein. 1062 66

Human Fibroblast Activation Protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein that acts as a dual-specificity dipeptidyl-peptidase (DPP) and collagenase in vitro. Its restricted expression pattern in embryonic mesenchyme, in wound healing and in reactive stromal fibroblasts of epithelial cancers, has suggested a role for the FAP protease in extracellular matrix degradation or growth factor activation in sites of tissue remodeling. The FAP homologue in Xenopus laevis has been reported to be induced in the thyroid hormone-induced tail resorption program during tadpole metamorphosis supporting a role for FAP in tissue remodeling processes during embryonic development. However, Fap-deficient mice show no overt developmental defects and are viable. To study the expression of FAP during mouse embryogenesis, a second Fap-deficient mouse strain expressing beta-Galactosidase under the control of the Fap promoter was generated by homologous recombination (Fap-/- lacZ mice). FAP deficiency was confirmed by the absence of FAP-specific dipeptidyl-peptidase activity in detergent-soluble extracts isolated from 17.5 d.p.c. Fap-/- lacZ embryos. We report that Fap-/- lacZ mice express beta-Galactosidase at regions of active tissue remodeling during embryogenesis including somites and perichondrial mesenchyme from cartilage primordia.
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PMID:Expression of the fibroblast activation protein during mouse embryo development. 1133 Aug 65

There is increasing evidence that the neutrophil chemoattractant proline-glycine-proline (PGP), derived from the breakdown of the extracellular matrix, plays an important role in neutrophil recruitment to the lung. PGP formation is a multistep process involving neutrophils, metalloproteinases (MMPs), and prolyl endopeptidase (PE). This cascade of events is now investigated in the development of lung emphysema. A/J mice were whole body exposed to cigarette smoke for 20 wk. After 20 wk or 8 wk after smoking cessation, animals were killed, and bronchoalveolar lavage fluid and lung tissue were collected to analyze the neutrophilic airway inflammation, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels. Lung tissue degradation was assessed by measuring the mean linear intercept. Additionally, we investigated the effect of the peptide L-arginine-threonine-arginine (RTR), which binds to PGP sequences, on the smoke-induced neutrophil influx in the lung after 5 days of smoke exposure. Neutrophilic airway inflammation was induced by cigarette smoke exposure. MMP-8 and MMP-9 levels, PE activity, and PGP levels were elevated in the lungs of cigarette smoke-exposed mice. PE was highly expressed in epithelial and inflammatory cells (macrophages and neutrophils) in lung tissue of cigarette smoke-exposed mice. After smoking cessation, the neutrophil influx, the MMP-8 and MMP-9 levels, the PE activity, and the PGP levels were decreased or reduced to normal levels. Moreover, RTR inhibited the smoke-induced neutrophil influx in the lung after 5 days' smoke exposure. In the present murine model of cigarette smoke-induced lung emphysema, it is demonstrated for the first time that all relevant components (neutrophils, MMP-8, MMP-9, PE) involved in PGP formation from collagen are upregulated in the airways. Together with MMPs, PE may play an important role in the formation of PGP and thus in the pathophysiology of lung emphysema.
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PMID:Cigarette smoke-induced lung emphysema in mice is associated with prolyl endopeptidase, an enzyme involved in collagen breakdown. 2111 44

The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE), and it is concomitantly degraded by extracellular leukotriene A4 hydrolase (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP, yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and can, thus, support a sustained neutrophilia. In this study, we sought to elucidate if an antiinflammatory system existed to degrade AcPGP that is analogous to the PGP-LTA4H axis. We demonstrate that AcPGP is degraded through a previously unidentified action of the enzyme angiotensin-converting enzyme (ACE). Pulmonary ACE is elevated during episodes of acute inflammation, as a consequence of enhanced vascular permeability, to ensure the efficient degradation of AcPGP. Conversely, we suggest that this pathway is aberrant in chronic obstructive pulmonary disease (COPD) enabling the accumulation of AcPGP. Consequently, we identify a potentially novel protective role for AcPGP in limiting pulmonary fibrosis and suggest the pathogenic function attributed to ACE in idiopathic pulmonary fibrosis (IPF) to be a consequence of overzealous AcPGP degradation. Thus, AcPGP seemingly has very divergent roles: it is pathogenic in its capacity to drive neutrophilic inflammation and matrix degradation in the context of COPD, but it is protective in its capacity to limit fibrosis in IPF.
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PMID:Angiotensin-converting enzyme defines matrikine-regulated inflammation and fibrosis. 2920 50


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