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)

Contractions of the rat uterus in response to trypsin, kallikrein, bradykinin, angiotensin II, oxytocin and acetylcholine, were abolished when an inside-out preparation was used. Sensitivity to Ba++, however, was preserved. In preparations in which the endometrium was mechanically removed, all above cited agonists elicited contractions. By treating the uterus with both collagenase and hyaluronidase, acetylcholine was able to induce a contraction when applied to the endometrium side of the uterus. The results show that a barrier for protease, peptides and acetylcholine is present in the mucosa of the rat uterus.
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PMID:Pharmacological demonstration of a barrier for protease, peptides and acetylcholine in the endometrium of the rat. 818 17

A cDNA coding for a new human matrix metalloproteinase (MMP) has been cloned from a cDNA library derived from a breast tumor. The isolated cDNA contains an open reading frame coding for a polypeptide of 471 amino acids. The predicted protein sequence displays extensive similarity to the previously known MMPs and presents all the structural features characteristic of the members of this protein family, including the well conserved PRCGXPD motif, involved in the latency of the enzyme and the zinc-binding domain (HEXGHXXXXXHS). In addition, this novel human MMP contains in its amino acid sequence several residues specific to the collagenase subfamily (Tyr-214, Asp-235, and Gly-237) and lacks the 9-residue insertion present in the stromelysins. According to these structural characteristics, the MMP described herein has been tentatively called collagenase-3, since it represents the third member of this subfamily, composed at present of fibroblast and neutrophil collagenases. The collagenase-3 cDNA was expressed in a vaccinia virus system, and the recombinant protein was able to degrade fibrillar collagens, providing support to the hypothesis that the isolated cDNA codes for an authentic collagenase. Northern blot analysis of RNA from normal and pathological tissues demonstrated the existence in breast tumors of three different mRNA species, which seem to be the result of the utilization of different polyadenylation sites present in the 3'-noncoding region of the gene. By contrast, no collagenase-3 mRNA was detected either by Northern blot or RNA polymerase chain reaction analysis with RNA from other human tissues, including normal breast, mammary fibroadenomas, liver, placenta, ovary, uterus, prostate, and parotid gland. On the basis of the increased expression of collagenase-3 in breast carcinomas and the absence of detectable expression in normal tissues, a possible role for this metalloproteinase in the tumoral process is proposed.
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PMID:Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. 820

Fetal membranes usually are released from the uterus between 2 and 6 postpartum hours. However, in a substantial percentage of cows (11%), fetal membranes are retained for several days. In part, failure of collagen breakdown seems to be related to retention of fetal membranes. Injections of 200,000 U of bacterial collagenase in 1,000 ml of physiologic saline solution via umbilical arteries (1 or 2) between 24 and 72 hours of retention caused release of retained fetal membranes in 23 of 27 cows (85%) with noninduced retained fetal membranes and in 10 of 14 cows (71%) with experimentally induced retained fetal membranes, within 36 hours after injection. Controls (n = 36) did not release retained fetal membranes within this time. Injections of collagenase via a jugular vein (2.2 x 10(6) U in 1,000 ml of physiologic saline solution), administered over a 30-minute period, caused release of retained fetal membranes within 36 hours in 3 of 6 cows with experimentally induced retained fetal membranes. Clinical complications did not follow treatments with collagenase. Umbilical injections of bacterial collagenase were highly effective in the treatment of retained fetal membranes in cows. The procedure is simple, safe, affordable, and can be completed in 25 minutes.
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PMID:Successful treatment of retained placenta with umbilical cord injections of collagenase in cows. 822 24

Synthesis of gap junction proteins (GJPs) and of collagenases in the rat uterus has been studied under two physiological conditions: various stages of the estrus cycle, and the early pregnancy period. The synthesis has been studied by incubating uterine horns in a short-term tissue culture medium containing radioactively-labeled amino acids, followed by a double antibody immunoprecipitation of the labeled proteins. After exposure of the media to either anti-collagenase IgG(s) or anti-GJPs IgG(s), the final immunoprecipitation was achieved with the use of goat anti-rabbit IgG. Collagenase(s) synthesis was found to reach the peak, during the estrus cycle, at the proestrus stage, while GJP synthesis reached the maximum during the estrus stage. In the preimplantation, pregnant, rat uterus the syntheses of both the proteins reached the respective peak activities on day 4 of pregnancy, about 24 h before the expected time of ovum implantation. A study of the literature reveals that this time coincides with a spurt in exposure of the progesterone dominated uterus to estradiol.
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PMID:Synthesis of gap junction proteins and collagenases in the preimplantation rat uterus. 823 99

Measurement of collagenolytic activity is of interest to a wide variety of investigators using mammalian tissue. In order to develop a method that would quantitate active collagenase from microquantities of human tissue, we employed zymography to the heart and uterus of neonatal, adult, and postpartum rats. Collagenase rapidly cleaves native collagen into two fragments, which at 37 degrees C form gelatin. Gelatin can also be hydrolyzed by collagenase, but at a slower rate, and therefore we used gelatin to quantitate the amount of collagenase present in heart and uterine tissue and developed a method for the direct extraction of collagenase from small quantities of rat myocardium. Our method was found to be comparable with the chemical method reported by Masui et al. (Anal Biochem 1977; 17:215-21). The enzyme, which was not detected in normal adult rat cardiac tissue, was found to exist entirely in latent form and demonstrated typical properties of a mammalian collagenase/gelatinase after activation by trypsin and plasmin. We observed a 60-80% increase in collagenase activity after activation by these proteases and estimated that there is approximately 5 +/- 2 pg of procollagenase per microgram of normal adult rat left ventricle. Collagenolytic activity in the postpartum rat heart was found to be slightly (approximately 2-5%) reduced when compared to the adult heart but it was increased in the neonatal heart and postpartum uterus. This method allows for the rapid quantitative and qualitative measurement of collagenase activity in a variety of tissues containing collagenase/gelatinase activity. Our results indicate that most collagenase in the myocardium exists in latent form.
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PMID:Direct extraction and estimation of collagenase(s) activity by zymography in microquantities of rat myocardium and uterus. 833 Mar 88

Two different methods of study have been employed in the analysis of the hormonal regulation of rat uterine collagenases. The first is concerned with the enzyme activity and the second, its synthesis. The data presented in this report reveal that the rat uterine collagenase is under the regulatory influence of both estradiol and progesterone. This fact is first exemplified by the observation that on Day 2 post-ovriectomy, a wave of collagenase synthesis takes place which influences the enzyme activity in the uterus during the next 3-4 days. This peak in collagenase synthesis disappeared in the uteri of rats subjected to ovariectomy and adrenalectomy simultaneously. It indicated that a hormone of adrenal origin was responsible for the enhanced synthesis and activity of collagenase in the uteri of ovariectomized rats. That the hormone involved was progesterone was shown by the subsequent experimental data. The estradiol-mediated enhancement in rat uterine collagenase activity has been shown to be inhibited by intraluminal exposure of the uteri to actinomycin D/cyclohexinmide, indicating the apparent influence of the hormone at the level of the collagenase gene.
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PMID:Hormonal regulation of rat uterine collagenase. 848 68

Collagens of most connective tissues are subject to continuous remodelling and turnover, a phenomenon which occurs under both physiological and pathological conditions. Degradation of these proteins involves participation of a variety of proteolytic enzymes including members of the following proteinase classes: matrix metalloproteinases (e.g. collagenase, gelatinase and stromelysin), cysteine proteinases (e.g. cathepsin B and L) and serine proteinases (e.g. plasmin and plasminogen activator). Convincing evidence is available indicating a pivotal role for matrix metalloproteinases, in particular collagenase, in the degradation of collagen under conditions of rapid remodelling, e.g. inflammation and involution of the uterus. Under steady state conditions, such as during turnover of soft connective tissues, involvement of collagenase has yet to be demonstrated. Under these circumstances collagen degradation is likely to take place particularly within the lysosomal apparatus after phagocytosis of the fibrils. We propose that this process involves the following steps: (i) recognition of the fibril by membrane-bound receptors (integrins?), (ii) segregation of the fibril, (iii) partial digestion of the fibril and/or its surrounding non-collagenous proteins by matrix metalloproteinases (possibly gelatinase), and finally (iv) lysosomal digestion by cysteine proteinases, such as cathepsin B and/or L. Modulation of this pathway is carried out under the influence of growth factors and cytokines, including transforming growth factor beta and interleukin 1 alpha.
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PMID:Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. 876 55

Human pregnancy is associated with extensive growth and remodelling of the uterus and placenta, and restructuring of these tissues during specific stages of gestation likely involves the degradative activity of various matrix metalloproteinases (MMPs). In this investigation, we used in situ hybridization and immunohistochemistry to identify the sites and cell source of collagenase-1 (MMP-1), stromelysin-1 (MMP-3), matrilysin (MMP-7), and 92 kDa gelatinase (MMP-9), a subgroup of MMPs with the combined ability to degrade essentially all matrix proteins. Human tissues were recovered from uncomplicated pregnancies at various gestational ages and from pregnancies complicated by chorioamnionitis, pre-eclampsia, and placenta accreta. Our results show prominent expression of all four MMPs in specific cells of human placentae involved in trophoblast invasion and placental maturation. Collagenase-1 and stromelysin-1 were detected in cells of the amnion, decidua, and chorionic villi at all stages of pregnancy. Ninety-two kilodalton gelatinase was present in granulocytes whenever present. Matrilysin was seen in cytotrophoblasts and syncytiotrophoblasts during early pregnancy but only in cytotrophoblasts by the third trimester. In addition, we found that matrilysin is over expressed and is produced by more cell types in placentae from pregnancies complicated by pre-eclampsia suggesting that the proteolytic activity of this MMP contributes to the pathology of this condition. We conclude that certain MMPs produced by resident cells of the human placenta, and in particular trophoblasts, participate in the physiological progress human gestation and parturition.
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PMID:Collagenase-I, stromelysin-I, and matrilysin are expressed within the placenta during multiple stages of human pregnancy. 891 3

Evidence indicates that matrix metalloproteinases (MMPs) are essentially involved in the postpartum involution of the uterus. As little information exists about the gene regulation of those MMPs in the uterus, this study aimed to characterize the time course of messenger RNA (mRNA) levels of rat collagenase (MMP-13) and matrilysin (MMP-7) in virgin, late pregnant (18th and 21st day), and postpartum rats (1, 2, 3, and 4 days postpartum). Rat collagenase (MMP-13) mRNA levels were very low in virgin and pregnant animals, but increased transiently 30-fold postpartum, reaching a maximum on the second day postpartum. The temporal course of mRNA levels of matrilysin (MMP-7) shows similarity with that of collagenase mRNA levels, but at any stage the abundance of matrilysin mRNA was at least 100-fold higher than that of collagenase. In virgin animals, matrilysin mRNA levels were dependent on the estrous cycle, being 3- to 4-fold higher in the estrous and diestrous stages than during metestrus. MMP-7 shows an approximately 25-fold induction when comparing the mRNA levels in late pregnancy and 2 days postpartum. In cervexes of virgin, pregnant, and postpartum groups, collagenase mRNA was not detectable. Matrilysin in cervix shows temporal mRNA expression similar to that in uterus, with a maximum on day 1 postpartum. In cervix, we found a 14-fold induction when comparing levels in late pregnancy and those 1 day postpartum. Taken together, our findings suggest that the increased activity of MMPs in the postpartum uterus is due to a strong increase in the mRNA levels of MMP-13 and MMP-7.
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PMID:Messenger ribonucleic acid levels of collagenase (MMP-13) and matrilysin (MMP-7) in virgin, pregnant, and postpartum uterus and cervix of rat. 894 Mar 67

Matrilysin was first discovered in the involuting rat uterus; it has also been known as uterine metalloproteinase, putative metalloproteinase (Pump-1), and matrix metalloproteinase 7 (MMP-7). It is the smallest member (28 kDa) of a family of 15 MMPs that together are able to degrade most of the macromolecules of the extracellular matrix. This family is briefly reviewed; all members are zinc metalloproteinases that occur in zymogen form with the active site zinc blocked by cysteine. Matrilysin can degrade a wide range of gelatins, proteoglycans, and glycoproteins of the matrix and can activate several other MMPs including collagenase. With respect to the uterus, matrilysin is localized to epithelial cells and varies in amount with the estrus cycle and is found in high levels during postpartum involution. There is evidence for a role in the last stage of cervical ripening and immediately postpartum. Induction of premature delivery by onapristone and prostaglandin E2 advances these changes in matrilysin. Regulation of the enzyme levels in the uterus are considered from four viewpoints: control of protein synthesis (particularly in response to hormones), activation of the proenzyme to functional protease, retention of enzyme by binding to matrix components such as heparan sulfate, and inhibition by natural inhibitors such as tissue inhibitor of metalloproteinases (TIMPs) and alpha 2-macroglobulin.
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PMID:Regulation of matrilysin in the rat uterus. 916 47


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