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)

Prolidase (EC 3.4.13.9) is a ubiquitously distributed imidodipeptidase that catalyzes the hydrolysis of C-terminal proline or hydroxyproline containing dipeptides. The enzyme plays an important role in the recycling of proline for collagen synthesis and cell growth. An increase in enzyme activity is correlated with increased rates of collagen turnover indicative of extracellular matrix (ECM) remodeling, but the mechanism linking prolidase activity and ECM is poorly understood. Thus, the effect of ECM-cell interaction on intracellular prolidase activity is of special interest. In cultured human skin fibroblasts, the interaction with ECM and, more specifically, type I collagen mediated by the beta 1 integrin receptor regulates cellular prolidase activity. Supporting evidence comes from the following observations: 1) in sparse cells with a low amount of ECM collagen or in confluent cells in which ECM collagen was removed by collagenase (but not by trypsin or elastase) treatment, prolidase activity was decreased; 2) this effect was reversed by the addition of type I collagen or beta 1 integrin antibody (agonist for beta 1 integrin receptor); 3) sparse cells (with typically low prolidase activity) showed increased prolidase activity when grown on plates coated with type I collagen or on type IV collagen and laminin, constituents of basement membrane; 4) the relative differences in prolidase activity due to collagenase treatment and subsequent recovery of the activity by beta 1 integrin antibody or type I collagen treatment were accompanied by parallel differences in the amount of the enzyme protein recovered from these cells, as shown by Western immunoblot analysis. Thus, we conclude that prolidase activity responded to ECM metabolism (tissue remodeling) through signals mediated by the integrin receptor.
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PMID:Prolidase activity in fibroblasts is regulated by interaction of extracellular matrix with cell surface integrin receptors. 932 22

Activity of lysosomal (cathepsins A,B,C,D and E) and nonlysosomal proteases (cathepsin G, elastase, collagenase, prolidase, prolinase) was evaluated in fibrosarcoma induced in rats by methylcholanthrene. No differences were found in the activity of the examined proteases in tumours of different size in the external, intermediate and central spheres of these tumours. Activity of cathepsins A,B,C,D,E and G, prolidase and prolinase was higher in the fibrosarcoma and activity of collagenase and elastase was lower than in the rat skin.
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PMID:Activity of lysosomal and nonlysosomal proteases of fibrosarcoma induced by methylcholanthrene. 958 82

Activity of lysosomal and nonlysosomal proteases and contents of protein and its degradation products in the blood serum of rats with methylcholantrene fibrosarcoma were evaluated. Activity of lysosomal proteases and prolidase and prolinase as well in the blood serum of rats with methylcholanthrene tumour did not differ from the activity of these enzymes in the blood serum of control rats. Only the activity of elastase and collagenase in the blood serum of rats with methylcholanthrene tumour especially with tumour of intermediate and big mass was increased. Content of total protein was decreased in the blood serum of rats with tumour of intermediate and big mass and contents of glycoproteins and alfa-amin nitrogen were increased in comparison to the blood serum of control rats.
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PMID:Activity of lysosomal and nonlysosomal proteases and contents of protein and its degradation products in the blood serum of rats with fibrosarcoma induced by methylcholanthrene. 958 83

Prolidase (EC 3.4.13.9) is an ubiquitously distributed imidodipeptidase that catalyzes the hydrolysis of dipeptides containing C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline for collagen synthesis and cell growth. We have shown previously that prolidase activity in normal human skin fibroblasts is regulated by the interaction of type I collagen with beta1 integrin receptor. In the present study, we investigate prolidase activity in MCF-7 cells and find it is only one-third of that in normal human skin fibroblasts. The relative difference in prolidase activity is corroborated by enzyme protein with Western immunoblot analysis. We propose that the decrease in prolidase activity is due to derangement of regulation by the collagen-beta1 integrin receptor axis. Supporting evidence comes from the following observations: (1) relative collagen content elaborated by MCF-7 cells as compared to fibroblasts is lower by 30% in sparse cells and by 80% at confluence; (2) collagenase treatment of both cell types results in decreased enzyme activity; (3) in contrast to fibroblasts, prolidase activity in MCF-7 cells is not stimulated by the addition of type I collagen or beta1 integrin antibodies (agonist for beta1 integrin receptor); and (4) in contrast to fibroblasts, MCF-7 cells express only trace amounts of beta1 integrin receptor as shown by Western immunoblot analysis. Thus, we conclude that depressed prolidase activity in MCF-7 cells may be a result of disturbances in signaling mediated by beta1 integrin-collagen interaction.
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PMID:Prolidase in human breast cancer MCF-7 cells. 961 59

Prolidase [EC 3.4.13.9] plays an important role in the recycling of proline for collagen synthesis and cell growth. The increase in the enzyme activity is correlated with the increased intensity of collagen turnover, thus reflecting the intensity of collagen metabolism. Since estrogens alter collagen metabolism, it can be assumed that the changes may be reflected by prolidase activity. The effects of estrogen and antiestrogen (tamoxifen on the prolidase and collagenase activities and collagen biosynthesis) were measured in the estrogen-receptor (ER)-positive breast cancer cell line. Estradiol stimulated collagen biosynthesis and extracellular prolidase and collagenase activities in cultured MCF-7 cells without an effect on collagen accumulation in the extracellular matrix produced by these cells. On the other hand, tamoxifen inhibited the estrogen-dependent stimulatory effect on collagen biosynthesis but did not inhibit the stimulatory effect of estrogen on prolidase and collagenase activities. The inhibitory effect of tamoxifen on estrogen-dependent stimulation of collagen synthesis in MCF-7 cells and lack of its effect on estrogen-dependent stimulation of prolidase and collagenase activities suggest that both processes (collagen synthesis and degradation) are independently regulated in MCF-7 cells, possibly through antagonist, agonist and other estrogen receptor-independent actions of tamoxifen. Increased extracellular prolidase activity in estrogen-stimulated MCF-7 cells indicates potential diagnostic value of tissue prolidase in determining the ER status of breast cancer.
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PMID:Estrogen-dependent regulation of prolidase activity in breast cancer MCF-7 cells. 1045 8

Prolidase [EC 3.4.13.9] is a ubiquitously distributed imidodipeptidase that catalyzes the hydrolysis of C-terminal proline-containing dipeptides. The enzyme plays an important role in the recycling of proline for collagen synthesis and cell growth. Although, the increase in the enzyme activity is correlated with increased rate of collagen turnover, the mechanism by which prolidase is regulated remain largely unknown. In the present study we found that phosphorylation of fibroblast's prolidase may be an underlying mechanism for up regulation of the enzyme activity. Supporting evidence comes from the following observations: (1) immunoprecipitated prolidase was detected as a phosphotyrosine protein as shown by western immunoblot analysis, (2) tyrosine kinase inhibitor-erbstatin induced (in a dose dependent manner) a decrease in prolidase activity in cultured human skin fibroblasts, (3) anti-phosphotyrosine antibody reduced and phosphotyrosine phosphatase 1B antibody (anti-PTP 1B) increased (in a dose dependent manner) the prolidase activity in extract of fibroblast's homogenate, (4) decrease in prolidase activity from collagenase treated or serum starved fibroblasts can be partially prevented by incubating fibroblast's homogenate extract with anti-PTP 1B antibody. These results provide evidence that prolidase is phosphotyrosine enzyme and suggest that the activity of prolidase may be up regulated by the enzyme phosphorylation.
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PMID:Phosphorylation of prolidase increases the enzyme activity. 1145 88

Several lines of evidence suggest that doxycycline, a semi-synthetic derivative of tetracycline, may be a useful agent in the treatment of osteoarthritis. It inhibits collagen synthesis and collagenase activity in hypertrophic chondrocytes, slowing the process of collagen turnover. However, the mechanism of doxycycline-induced inhibition of these processes has not been established. We considered prolidase, an enzyme involved in collagen metabolism, as a possible target for the doxycycline-induced inhibition of collagen synthesis. Cultured human skin fibroblasts, specialized for collagen synthesis, were used as model cells. Prolidase [E.C. 3.4.13.9] is a manganese-dependent cytosolic exopeptidase that cleaves imidodipeptides containing C-terminal proline, thus providing large amounts of proline for collagen resynthesis. Enzyme activity is regulated through the beta1 integrin receptor. Therefore, we compared the effect of doxycycline on prolidase activity and expression, collagen biosynthesis, gelatinolytic activity and beta1 integrin expression in 24-h treated cultured human skin fibroblasts. We found that doxycycline induced coordinately inhibition of prolidase activity and collagen biosynthesis (IC50 at about 150 microg/ml) and gelatinolytic activity in cultured human skin fibroblasts. The inhibitory effect of doxycycline on the processes was not due to the cytotoxicity of this drug, as shown in the cell viability tetrazoline test. However, an inhibitory effect of the drug on DNA synthesis was observed (IC50 at about 100 microg/ml). The decrease in prolidase activity in fibroblasts treated with doxycycline was not accompanied by any differences in the amount of prolidase or beta1 integrin recovered from these cells, as shown by Western immunoblot analysis. This suggests that the doxycycline-induced down-regulation of prolidase is a post-translational event. The data presented here raise the possibility that the doxycycline-induced decrease in collagen biosynthesis is mostly due to the inhibition of prolidase activity.
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PMID:Doxycycline-induced inhibition of prolidase activity in human skin fibroblasts and its involvement in impaired collagen biosynthesis. 1169 59

Quantitative collagen determinations demonstrate an increase of approximately 800 per cent in the collagen content of the human uterus at term as compared with the non-pregnant state. Following parturition, there is a rapid resorption of collagen. The amount of collagen which disappears from the post partum uterus is approximately 53 gm. By the 8th day post partum, the human uterus has lost approximately 72 per cent of the total collagen which was present at term. The slopes of curves depicting alterations in collagen content of the uterus of the rat and human are virtually identical, despite the marked differences in the length of the gestational periods of the two species. The alterations in the collagen content of the human uterus during pregnancy and involution closely follow changes in total uterine weight. There is a slight decrease in per cent collagen content of the uterus during pregnancy, and an increase in the water content of the post partum uterus. Approximately 97 per cent of the collagen which is present in the human uterus at term is of the so called "insoluble" type. The physiological resorbability of uterine collagen, as evidenced by its post partum dissolution, cannot therefore be correlated with its in vitro solubility characteristics. No collagenase was demonstrable in the myometrium of post partum uteri. A 2 day post partum uterus was found to contain an enzyme which slowly degraded gelatin at pH 3.85 but was virtually inactive at pH 7,0. There is an increase in myometrial prolidase activity of approximately 75 per cent, commencing 2 days post partum. Prolidase activity remains elevated until the 8th day post partum, and subsequently falls to almost normal levels by the 5th post partum week. During the process of involution, the post partum uterus shows histological evidence of edema and partial destruction of its reticular framework.
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PMID:Alteration in the collagen content of the human uterus during pregnancy and post partum involution. 1447 28

The aim was to investigate the suppressive effect of bicyclol on hepatic fibrosis induced by dimethylnitrosamine (DMN) in mice and the mechanism of its action. Hepatic fibrosis was established by intraperitoneal injection of 8 mg kg(-1) day(-1) on three consecutive days of each week for 4 or 5 weeks. In the prophylactic experiment, bicyclol (100 and 200mg.kg(-1)) was administered by gavage in association with DMN injection. For the therapeutic experiment, mice were firstly injected with DMN for 5 weeks as in the prophylactic experiment, and then the mice in drug groups were orally administered bicyclol (100 and 200mg.kg(-1)) once daily for 5 weeks. As a result, the levels of alanine aminotransferase (ALT), total bilirubin, hydroxyproline (Hyp), prolidase, tumor necrosis factor-alpha (TNFalpha), transforming growth factor beta-1 (TGFbeta(1)), type I collagen in serum and the score of liver fibrosis all significantly increased in the hepatic fibrosis model group in comparison with those in control group. The treatment with bicyclol markedly reduced all the above criteria. Bicyclol also attenuated the decrease of body weight of mice, serum total protein and albumin. In addition, bicyclol treatment inhibited liver TGFbeta(1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA expression in the prophylactic experiment. Similarly, bicyclol reduced TIMP-1 levels in liver and serum and increased collagenase activity in the liver in the therapeutic experiment. The result suggest that bicyclol attenuates DMN-induced hepatic fibrosis in mice. Its mechanisms of action may be related to the hepatoprotective and anti-inflammation properties, the down-regulation of liver TGFbeta(1) and TIMP-1 expression and the increase of net collagenase activity in liver.
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PMID:Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action. 1660

The aim of the present study was to identify bioactive compounds stimulating collagen biosynthesis with potential for osteogenesis imperfecta (OI) type I pharmacological therapy. Of the compounds tested, apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide and pectolinarin at 30 microM were found to significantly induce collagen type I synthesis in OI fibroblasts without an effect on the overall protein synthesis. None of the compounds displayed any toxicity at that concentration. Secretion of collagen into media was not affected by apigenin 7-O-glucuronide and was slightly increased in cells treated with apigenin 7-O-methylglucuronide and pectolinarin. Furthermore, procollagen secreted by treated cells underwent a more rapid processing into collagen as compared with control untreated cells. In addition, we elucidated the possible mechanism involved in their action. Stimulation of collagen biosynthesis was not due to an increase in cell proliferation, because no differences in DNA content between the compound-treated and untreated cells were observed. Since flavonoids are known as strong inhibitors of metalloproteinases degrading matrix proteins, the increased level of collagen could result from the inhibition of their activity. However, the compounds with a stimulatory effect on collagen synthesis did not influence the activities of collagenase type I, gelatinases A and B, and stromelysin. On the contrary, all compounds stimulated the activity of prolidase which catalyzes the final step of collagen degradation and plays an important role in collagen biosynthesis. Stimulation of collagen synthesis and prolidase activity by apigenin 7-O-glucuronide was accompanied by an increase in IGF-I receptor expression. In contrast, the compounds apigenin 7-O-methylglucuronide and pectolinarin which normalized collagen synthesis in OI cells may exert their effects through beta1-integrin-mediated signaling.
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PMID:Stimulation of collagen biosynthesis by flavonoid glycosides in skin fibroblasts of osteogenesis imperfecta type I and the potential mechanism of their action. 1798 99


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