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)

An appropriate balance of matrix synthesis and degradation is required for normal morphogenesis and maintenance of tissue architecture. Extracellular matrix molecules and their receptors, as well as proteinases and their inhibitors, are all involved in matrix remodeling. This report examines the idea that extracellular matrix receptors can regulate matrix remodeling. Rabbit synovial fibroblasts and human embryonic lung fibroblasts (MRC-5) were cultured under two sets of conditions. First, they were plated in serum and allowed to establish an extracellular matrix over a 48 h period. Rat monoclonal antibody to the alpha 5/beta 1 integrin fibronectin receptor or normal rat IgG was added to the medium and the expression of the metalloproteinases was examined. Cells treated with anti-alpha 5/beta 1 expressed procollagenase and prostromelysin, whereas the control cells did not. In both cases the cells were well spread and maintained a well-organized cytoskeleton. In the second condition, cells were plated in serum-free medium on intact fibronectin, anti-alpha 5/beta 1, or fragments of fibronectin that contained the cell-binding domain. Cells attached and spread on all these substrates in a fibronectin receptor-dependent manner. They expressed collagenase and stromelysin on anti-alpha 5/beta 1 and on several fibronectin fragments, but not on intact fibronectin. These data support the hypothesis that the fibronectin receptor can exist in more than one functional state and that these functional states provide information that influences gene expression. Adhesion and spreading are supported by all states, whereas only a subset permits collagenase and stromelysin expression.
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PMID:Signal transduction via the fibronectin receptor: do integrins regulate matrix remodeling? 128 60

Human vascular smooth muscle cells have been used to assess the implied role of connective tissue microfibrils as cellular ligands. Preparations of intact high-M(r) microfibrillar assemblies of collagen VI and of fibrillin, respectively, were isolated from foetal bovine skin and used as ligands in cell attachment and spreading assays. Intact collagen VI microfibrils were capable of mediating cell attachment and partial spreading. Cell attachment assays using ligands composed of defined collagen VI fragments generated by pepsin or bacterial collagenase digestions demonstrated that both the triple-helical and non-collagenous domains of collagen VI had cell adhesion activity, although at reduced levels relative to intact microfibrils. Fibronectin was identified as a modulator of intact collagen VI microfibril-mediated cell attachment. These observations are indicative of complex multiple interactions between collagen VI microfibrils and smooth muscle cells. Purified fibrillin-containing microfibrils were also shown to support smooth muscle cell adhesion. Both pepsin-resistant and pepsin-sensitive domains of fibrillin exhibited some cell attachment activity, but at reduced levels relative to the intact fibrillin microfibrils. These data provide the first direct evidence of a physiological role for intact microfibrillar assemblies in cell-matrix interactions, and the involvement of integrin cell surface receptors containing the beta 1 subunit.
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PMID:Attachment of human vascular smooth muscles cells to intact microfibrillar assemblies of collagen VI and fibrillin. 147 46

The present study determined whether a developmental increase in placental low density lipoprotein (LDL) uptake occurred in baboon pregnancy, which was related to the increasing concentrations of estrogen typical of advancing gestation. LDL uptake was determined on collagenase-dispersed placental trophoblast cells purified via 50% Percoll gradient centrifugation and obtained from baboons between days 55-178 of gestation (i.e. the last two-thirds of gestation; term = 184 days). The majority of cells in the 50% Percoll-isolated fraction used to determine LDL uptake were syncytiotrophoblasts at all stages of gestation examined, as determined by immunohistochemical staining for syncytiotrophoblast-specific placental lactogen and pregnancy-specific-beta 1-glycoprotein. Placental LDL uptake, as determined by Scatchard analysis, increased progressively during the last two-thirds of gestation and was correlated (r = 0.87, P less than 0.001; curvilinear regression) with gestational age. Mean +/- SE LDL uptake early in pregnancy on days 55-58 was 1.9 +/- 0.2 ng/micrograms cell protein (n = 3). Placental LDL uptake (ng/microgram cell protein) at midgestation on days 94-104 (2.8 +/- 0.2; n = 5) increased to a value late in gestation on days 159-178 (14.6 +/- 1.0; n = 13), which was approximately 5-fold greater (P less than 0.001) than at midgestation, whereas uptake on days 128-138 was intermediate in value (8.3; n = 2) between the latter two periods. The apparent dissociation constant for placental LDL uptake was lower (P less than 0.01) at midgestation (0.33 micrograms/ml) than late in gestation (0.81 micrograms/ml). Placental LDL degradation, which depends on uptake, also increased with advancing stages of pregnancy, and was correlated (r = 0.74, P less than 0.01; curvilinear regression) with gestational age. Overall mean peripheral serum LDL cholesterol concentration was 46.5 +/- 1.7 mg/dl between days 50-170 of gestation. However, there was no significant change in serum LDL levels during this period. Maternal peripheral serum estradiol concentrations increased from 0.3 ng/ml on day 55 to an initial peak of approximately 3.5 ng/ml on days 70-80, then declined to approximately 1.0 ng/ml at midgestation. Estradiol then increased progressively throughout the remainder of pregnancy to maximal values of over 6 ng/ml late in gestation. In summary, there was a progressive increase in placental LDL uptake with advancing stages in the last two-thirds of baboon pregnancy, which was associated with a concomitant rise in maternal serum estradiol concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental increase in placental low density lipoprotein uptake during baboon pregnancy. 153 17

We have previously shown that placental low density lipoprotein (LDL) uptake is decreased in baboons treated with antiestrogen and we have proposed, therefore, that estrogen regulates placental LDL uptake and use during primate pregnancy. In the present study, an alternate in vivo approach was employed to determine whether restoration of estrogen in animals in which the formation of estrogen was decreased would reverse the decline in LDL uptake. Placental estrogen was suppressed by removing the fetus (fetectomy) and thus adrenal androgens on day 100 of baboon gestation (term is 184 days). Placental LDL uptake was determined on day 160 after fetectomy alone, and after fetectomy and sc administration of the estrogen precursor androstenedione (50 to 150 mg every 10 days). Placental cells (10(6] were dispersed with 0.1% collagenase, isolated via 50% Percoll gradient centrifugation, then incubated at 37 C for 12 h in medium 199 with 10-100 micrograms [125I]LDL and LDL uptake (i.e. binding and internalization) determined by Scatchard analysis. In intact baboons and animals that had undergone fetectomy, syncytiotrophoblasts predominated and formed a continuous surface covering of the placental villi. Moreover, placental cells of intact and fetectomized baboons isolated on 50% Percoll consisted primarily of syncytiotrophoblasts, as evidenced by their immunohistochemical reaction with antisera against placental lactogen and pregnancy-specific-beta 1-glycoprotein. Serum estradiol in untreated baboons increased with advancing gestation and mean (+/- SE) concentrations were 1.29 +/- 0.04 ng/ml on days 101-160 of gestation. Placentas remained in situ and viable after fetectomy, but serum estradiol decreased to 0.24 +/- 0.02 ng/ml, or 19% of normal (P less than 0.01). Androstenedione restored serum estradiol after fetectomy to a mean of 0.69 +/- 0.03 ng/ml on days 101-160, or 53% of normal. Specific LDL uptake (nanograms per microgram protein) by placental cells after fetectomy alone (3.2 +/- 0.4) was 22% (P less than 0.001) of controls (14.4 +/- 1.2). Androstenedione increased (P less than 0.005) LDL uptake after fetectomy to a value (8.8 +/- 1.2) that was 61% of normal. LDL degradation, which depends on uptake, was 59 +/- 1% of normal after fetectomy and restored with androstenedione treatment to 94 +/- 2% of normal. Apparent dissociation constants (microgram/ml) for LDL uptake were similar after fetectomy (0.38), and fetectomy and androstenedione treatment (0.41), but lower (P less than 0.01) than in intact animals (0.80).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of placental low density lipoprotein uptake in baboons by estrogen. 198 38

The roles of polypeptide growth factors in promoting wound healing and in directing the specificity and sequence of responses of different tissues in wounds are little understood. We investigated the influence of four growth factors on the rates of healing of a novel full thickness dermal ulcer placed on an avascular base in the rabbit ear. The wound model precludes significant wound contraction and requires new granulation tissue and epithelial cells for healing to originate centripetally. 5 micrograms (7-31 pmol/mm2) of platelet-derived growth factor-B chain (PDGF-BB), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) applied locally at the time of wounding resulted in a twofold increase in complete reepithelialization of treated wounds (PDGF-BB, P = 0.02 chi square analysis; bFGF, P = 0.04; EGF, P = 0.05); transforming growth factor (TGF)-beta 1 significantly inhibited reepithelialization (P = 0.05). Both PDGF-BB and TGF-beta 1 uniquely increased the depth and area of new granulation tissue (P less than 0.005), the influx of fibroblasts, and the deposition of new matrix into wounds. Explants from 7-d old PDGF-BB-treated wounds remained metabolically far more active than controls, incorporating 473% more [3H]thymidine into DNA (P = 0.05) and significantly more [3H]leucine and [3H]proline into collagenase-sensitive protein (P = 0.04). The results establish that polypeptide growth factors have significant and selective positive influences on healing of full thickness ulcers in the rabbit.
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PMID:Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. 199 53

Circulating AC levels as well as antibodies against AC-protein adducts are increased in non-alcoholic liver injury. To identify the adducts, we used rats with CCl4-induced cirrhosis. Liver subcellular fractions were analyzed by immunochemical staining of protein slot blots and of electrophoretically separated proteins, transferred to nitrocellulose, using AC-protein adduct-specific antibodies. One reactive protein of about 200 kD was detected in the liver soluble fraction and in the cytosol of isolated hepatocytes and, to a lesser extent in the liver microsomes of CCl4-treated rats; in control animals, this reactivity was much weaker. The immunopositive AC adduct co-migrated with the beta 1,2 dimer of rat collagen type I; it was sensitive to digestion by a highly purified collagenase and also reacted with anti-rat collagen type I-specific IgG. In addition, comparison of peptides of the CNBr-digested, immunoprecipitated AC adduct with those of rat collagen type I revealed a high degree of similarity. Thus, AC adduct formation occurs in liver injury of non-alcoholic origin, and a target protein appears to be related to collagen type I, most likely the procollagen precursor.
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PMID:Acetaldehyde-collagen adducts in CCl4-induced liver injury in rats. 217 75

Acting alone or in concert with pituitary gonadotropins, catecholamines have recently been shown to enhance androgen production by ovarian theca-interstitial cells. It is the objective of the in vitro studies reported herein to further characterize this catecholaminergic activity as well as to type and subtype the putative adrenergic recognition sites mediating this phenomenon. Treatment of collagenase-processed whole ovarian dispersates or highly enriched (greater than 90%) theca-interstitial cells from immature rats with norepinephrine (10(-6) M) resulted in a 2.0-fold increment in the accumulation of androsterone (3 alpha-hydroxy-5 alpha-androstane-17-one), the main androgenic steroid identified in culture medium by HPLC. Qualitatively similar stimulation was obtained using beta (isoproterenol)- but not alpha (methoxamine)-selective adrenergic agonists. Moreover, combined treatment with both norepinephrine (10(-6) M) and hCG (1 ng/ml) unmasked a synergistic interaction subject to stereospecific blockade by beta (propranolol)- but not alpha (phentolamine)-selective adrenergic antagonists. Further probing with subtype-selective adrenergic ligands revealed terbutaline (a beta 2-selective agonist) to enhance androgen biosynthesis, with dobutamine (a beta 1-selective agonist) having little or no effect. Moreover, a beta 2 (ICI-118406)- but not a beta 1 (ICI-89406)-selective adrenergic antagonist yielded dose-dependent inhibition of the isoproterenol effect. Unaccounted for by either enhanced cellular growth or an alteration of the overall steroidogenic pattern, catecholaminergically stimulated androgen biosynthesis proved time and dose dependent but independent of the hCG dose (0.1-10 ng/ml) employed. Binding of [125I]iodocyanopindolol to highly enriched theca-interstitial cells proved stereoselective and saturable, displaying a single class (Hill coefficient = 0.96 +/- 0.01) of high affinity (Kd = 5.6 X 10(-11) M), low capacity (1219 +/- 317 sites/cell) binding sites. The rank order of competitive potencies of selective adrenergic ligands (beta 2 greater than beta 1 greater than alpha), was consistent with a beta 2-adrenergic receptor subtype. Taken together, these findings suggest that catecholaminergic stimulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic recognition sites, the role of which may now be studied.
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PMID:Adrenergic regulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic theca-interstitial cell recognition sites. 283 Oct 35

The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.
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PMID:Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells. 286 1

Recent studies have shown that beta-adrenergic agents stimulate steroidogenesis and cyclic AMP formation in mouse Leydig cells in culture. To obtain information about the possible presence and the characteristics of a beta-adrenergic receptor in rat testicular interstitial cells, the potent beta-adrenergic antagonist [125I]cyanopindolol (CYP) was used as ligand. Interstitial cells prepared by collagenase dispersion from rat testis were incubated with the ligand for 2 h at room temperature. [125I]cyanopindolol binds to a single class of high affinity sites at an apparent KD value of 15 pM. A number of sites of 6,600 sites/cell is measured when 0.1 microM (-) propranolol is used to determine non-specific binding. The order of potency of a series of agonists competing for [125I]cyanopindolol binding is consistent with the interaction of a beta 2-subtype receptor: zinterol greater than (-) isoproterenol greater than (-) epinephrine = salbutamol much greater than (-) norepinephrine. In addition, it was observed that the potency of a large series of specific beta 1 and beta 2 synthetic compounds for displacing [125I]cyanopindolol in rat interstitial cells is similar to the potency observed for these compounds in a typical beta 2-adrenergic tissue, the rat lung. For example, the potency of zinterol, a specific beta 2-adrenergic agonist, is 10 times higher in interstitial cells and lung than in rat heart, a typical beta 1-adrenergic tissue. Inversely, practolol, a typical beta 1-antagonist, is about 50 times more potent in rat heart than in interstitial cells and lung.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of beta-adrenergic receptors in dispersed rat testicular interstitial cells. 303 Sep 90

Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5-2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED50 of 1.4 and 1.5 nM, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (-)isoproterenol greater than (-)epinephrine equals (-)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nM, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 microM. (-)Isoproterenol stimulation of aldosterone production was potently inhibited by the beta-adrenergic antagonists (-)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nM, respectively. The alpha-adrenergic antagonists prazosin, yohimbine, and phentolamine only weakly inhibited (-)isoproterenol stimulation with potencies of 5, 13, and 140 microM, respectively. The potent beta 2-adrenergic antagonist ICI 118.551 and the weaker beta 1-adrenergic antagonist atenolol were roughly equipotent with potencies of 0.27 and 0.44 microM, respectively. Addition of the phosphodiesterase inhibitor Ro 20-1724 at 10 microM doubled the maximum stimulation effect of (-)isoproterenol without changing the potency of the catecholamine or the basal level of aldosterone secretion, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation. These results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells. The physiological significance of direct beta-adrenergic stimulation of aldosterone production is currently being assessed.
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PMID:Direct beta-adrenergic stimulation of aldosterone secretion in cultured bovine adrenal subcapsular cells. 614 9


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