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)

Exposure of rat epididymal fat pad to phorbol 12-myristate 13-acetate (TPA), an activator of protein kinase C, results in an 85% increase in isoproterenol-stimulated cyclic AMP (cAMP) accumulation, an effect which was antagonized by H7, a protein kinase C inhibitor. This promoting action of TPA appears to be related to (i) an increase in the catalytic activity of adenylate cyclase, (ii) an increase in the maximal response of adenylate cyclase to fluoride and guanylimidodiphosphate (GppNHp) with no change in the EC50 value for GppNHp, and (iii) a reduction of the isoproterenol-stimulated low-Km cAMP phosphodiesterase activity present in the 30,000 g pellet of fat pad homogenates. In contrast with fat pads, exposure of isolated rat fat cells to TPA failed to influence their adenylate cyclase response to GppNHp and their cAMP accumulation and lipolysis. However, the other alterations caused by TPA in fat pads were still observed in fat cells. These results suggest that (i) the major alteration responsible for the promoted isoproterenol-stimulated cAMP response observed in fat pads after exposure to TPA is an increased interaction between the alpha s subunit of Gs and the catalytic site of adenylate cyclase and (ii) this increased interaction is dependent on protein kinase C activation and is abolished by collagenase digestion.
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PMID:Differential modulation of the adenylate cyclase/cyclic AMP stimulatory pathway by protein kinase C activation in rat adipose tissue and isolated fat cells. Influence of collagenase digestion. 165 98

To determine whether spontaneous contractile activity affected the expression of myosin heavy chain isoenzymes in cultured neonatal rat heart cells, ventricular myocytes were isolated from 2-day-old rat pups by collagenase digestion and cultured for 24-96 h in the presence and absence of verapamil (10 microM), KCl (50 mM), or dihydropyridine receptor antagonists that produced contractile arrest. Inhibition of spontaneous contractile activity was associated with significant reductions in total myosin heavy chain (MHC) content and synthetic rates. Electrophoretic analysis of MHC isoenzymes indicated that MHC-beta protein rapidly disappeared from arrested cells, whereas MHC-alpha isoenzyme levels were less affected. In association with these protein changes, mRNA transcript levels for MHC-beta were markedly reduced in quiescent cells, whereas mRNA transcript levels for several other contractile protein genes were relatively less affected. Inhibition of contractile activity and MHC-beta expression were reversible upon removal of the arresting agents. Furthermore, the decrease in MHC-beta mRNA levels in arrested myocytes could be prevented by direct activation of protein kinase C with phorbol 12-myristate 13-acetate (without restoration of contractile activity). Conversely, MHC-beta mRNA levels in beating cells were reduced by treatment with staurosporine (a selective protein kinase C inhibitor). Thus contractile arrest (produced by either L-channel blockade or membrane depolarization) inhibited the accumulation of MHC-beta in cultured neonatal rat heart cells via a pretranslational mechanism. These effects may occur in response to the modulation of signaling system(s) involving mechanical "stretch" transduced via protein kinase C.
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PMID:Contractile activity modulates myosin heavy chain-beta expression in neonatal rat heart cells. 171 69

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Intraluminal TPA treatment caused increased BEAS-2B cell proliferation and downgrowth into the tracheal stroma. In an in vitro invasion assay, TPA enhanced the invasive capacity of BEAS-2B cells 20- to 25-fold. A similar result was observed with diacylglycerol (DAG), an endogenous activator of protein kinase C, and the effects of TPA and DAG were abolished by simultaneous treatment with H-7, a protein kinase C inhibitor. TPA induced type IV collagenolysis, and this effect also was prevented by H-7. These data are consistent with the hypothesis that TPA causes these cells to become invasive by inducing collagenase activity and that this effect is mediated via protein kinase C.
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PMID:Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-O-tetradecanoyl-phorbol-13-acetate and diacylglycerol. 255 20

In order for T cells to exit the circulatory system, traverse the endothelial basement membrane, and arrive in target tissues, these cells must attach to and degrade basement membrane proteins. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to stimulate lymphoid cell adhesion to basement membrane components. We have used TPA to study the ability of human lymphoid cells to secrete type IV collagenases, enzymes capable of degrading basement membrane proteins. Here, we found that human primary T cells and H-9 lymphoid cells synthesize the 92 kDa type IV collagenase (gelatinase B) and TPA stimulates the synthesis and secretion of this protease. Peak TPA-stimulated gelatinase B secretion and mRNA accumulation were observed 9 hours after TPA treatment, while the peak adhesion to type IV collagen was observed only 3 hours after TPA treatment. The protein kinase C inhibitor, H-7, inhibited TPA-stimulated gelatinase B secretion. Both the primary T cells and H-9 lymphoid cells also expressed the mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1). These data demonstrate that TPA-stimulated lymphoid cells adhere to type IV collagen and subsequently synthesize and secrete gelatinase B and TIMP-1. We conclude that lymphoid cell extravasation may involve cellular employment of adhesion mechanisms prior to degradation of the matrix, which is similar to the process of extravasation used by metastatic cells.
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PMID:Human T lymphocytes synthesize the 92 kDa type IV collagenase (gelatinase B). 825 76

The interstitial collagenase produced by the rat growth plate chondrocytes is the homologue of the human collagenase-3, or matrix metalloproteinase-13. This enzyme is responsible for the loss of collagen during hypertrophy of chondrocytes and for the degradation of transverse septa in long bone growth. Rachitic rats (42 days, male Sprague-Dawley) had an 8-fold higher level of collagenase mRNA in the hypertrophic versus proliferative zone of growth plate cartilage. Intramuscular injection of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 1.0 micrograms/kg body weight) in rachitic rats increased collagenase mRNA another 1.5-fold in the hypertrophic zone. The regulation of collagenase gene by 1,25-(OH)2D3 and interleukin (IL)-1 beta in cultured proliferative chondrocytes was studied by means of steady-state mRNA and half-life determination of mRNA using the transcriptional inhibitor actinomycin D, and nuclear run-on transcription analyses. Treatment of cells with 1,25-(OH)2D3 (10(-6) M) and IL-1 beta (2 ng/ml) increased collagenase mRNA 8- and 13-fold, respectively. Additionally, the collagenase mRNA half-life was increased by 1,25-(OH)2D3 and IL-1 beta. In the presence of a protein kinase C inhibitor, staurosporine, 1,25-(OH)2 D3 induction of collagenase mRNA was blocked. Here the addition of phorbol 12-myrisate 13-acetate (PMA) to activate protein kinase C increased collagenase mRNA 10-fold. However, in the presence of staurosporine (50 nM), PMA induction was blocked, whereas IL-1 beta was not. IL-1 beta is known to activate several phosphorylation pathways. Okadaic acid (500 nM), a protein phosphatase inhibitor, increased the relative collagenase mRNA abundance 10-fold. The rate of the rat collagenase gene transcription in nuclei was increased with 1,25-(OH)2D3, IL-1 beta and okadaic acid. In separate experiments, the collagenase promoter was ligated to a reporter plasmid and the plasmid was transfected into chondrocytes. The results showed that 1,25-(OH)2D3, IL-1 beta, and PMA increased reporter activity 2.5-, 2.8-, and 3.27-fold, respectively. Thus, there are multiple nuclear and cytoplasmic mechanisms by which cartilage modulators regulate rat interstitial collagenase gene expression.
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PMID:Regulation of rat interstitial collagenase gene expression in growth cartilage and chondrocytes by vitamin D3, interleukin-1 beta, and okadaic acid. 897 56

Calcium-tolerant rabbit cardiomyocytes were isolated using retrograde aortic perfusion with a nominally calcium-free, collagenase buffer. In vitro ischemic preconditioning was induced by a 10-min episode of ischemic pelleting, followed by a 15-min post-incubation and a prolonged period of ischemic pelleting. Injury was assessed by determination of cell contracture and trypan blue permeability following hypotonic swelling and correlated with metabolic assays of lactate and adenine nucleotides. The protein phosphatase PP1/2A inhibitor calyculin A and PP2A-selective fostriecin protected isolated rabbit cardiomyocytes from lethal injury after a 10-min pre-incubation and when added late into ischemic pellets after a delay of 75 min. At the time of late drug addition, cells were severely ATP-depleted and in rigor contracture. Protection with Calyculin A from 1 nM to 1 microM was dose-related. Cells pre-incubated with 10 nM to 10 microM fostriecin 10 min prior to ischemic pelleting were protected with an EC50 approximating 71 nM, implying protection at a PP2A-selective dose. The selective protein kinase C inhibitor, calphostin C, blocked ischemic preconditioning protection but not protection from 1 microM calyculin A. Protection of severely ischemic cardiomyocytes following protein phosphatase inhibition appears not to require PKC activity or ATP conservation. Pre-incubation of cells with calyculin A induced high levels of phosphorylation in p38 mitogen activated protein kinase (MAPK), as compared to the ischemia-induced phosphorylation observed in the untreated group only at 30 min of ischemia, providing evidence of protein phosphatase activity in cardiomyocytes. Pharmacological protection in late ischemia has been demonstrated, but the mechanism of protection is undetermined.
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PMID:Protein phosphatase inhibitors calyculin A and fostriecin protect rabbit cardiomyocytes in late ischemia. 950 Aug 65

Endothelin (ET)-1 is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca(2+) in the myocardium. The object of this study was to examine 1) the influence of ET(A) and ET(B) receptor subtypes, and 2) the role of the phospholipase C (PLC) pathway in mediating ET-1-induced contraction. Left ventricular cardiomyocytes were isolated from the hearts of New Zealand White rabbits (2-2.5 kg) by the use of Langendorff perfusion with collagenase. Cardiomyocyte function was examined during unloaded, electrically stimulated (0.5 Hz) contractions with a video-edge detection system. ET-1 increased cell shortening with greater potency than ET-3: mean EC(50) values were 1.1 x 10(-11) and 2.6 x 10(-10) M, respectively. With the same order of potency, ET-1 and ET-3 increased (P <.05) velocity of cell shortening. The ET(A) receptor-selective antagonist ABT-627 shifted the ET-1-induced cell shortening response curve to the right with a pA(2) value of 10.3. The ET(B) receptor-selective antagonist A-192621 (10(-8)-10(-7) M) did not alter the concentration-response of ET-1. Moreover, the ET(B) receptor-selective agonist sarafotoxin 6c did not have any effect on cell shortening over the concentration range of 10(-11) to 10(-7) M. ET-1 in the presence of the PLC inhibitor U-73122 did not alter the contractile amplitude. However, ET-1 in the presence of the protein kinase C inhibitor bisindolylmalemide increased cell shortening. These findings indicate that 1) the ET(A) receptor subtype, and not the ET(B) receptor subtype, mediates the positive inotropic effect of ET-1, and 2) the response of ET-1 is mediated by a PLC pathway, but not through protein kinase C, in ventricular cardiomyocytes isolated from rabbit myocardium.
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PMID:Endothelin(A) receptor subtype mediates endothelin-induced contractility in left ventricular cardiomyocytes isolated from rabbit myocardium. 1094 58

Gastric infection with Helicobacter pylori is associated with hypergastrinemia. Platelet activating factor (PAF) is produced in H. pylori-infected mucosa. The effects of PAF on gastrin release from cultured antral rabbit G cells were examined. Rabbit antral G-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation. After 40 hr in culture, gastrin release in response to PAF was assessed. PAF stimulated gastrin release in a dose-dependent manner. A maximal release of 67% above basal was seen with PAF at 100 nM. PAF also enhanced the gastrin release stimulated by forskolin and bombesin. PAF-stimulated gastrin release was abolished by a PAF-receptor antagonist. Gastrin release stimulated by PAF was abolished by chelation of intra- or extracellular calcium or the L-type calcium channel inhibitor verapamil as well as by the protein kinase C inhibitor chelerythrine. Platelet-activating factor may contribute to the hypergastrinemia of H. pylori infection by stimulating gastrin release from G cells. PAF-stimulated gastrin release involves influx of extracellular calcium via L-type channels and activation of protein kinase C.
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PMID:Effect of platelet-activating factor on gastrin release from cultured rabbit G-cells. 1128 66

Phospholipase C secreted by bacterial pathogens has been identified as a virulence factor in several human diseases and has been implicated in impeding wound healing. The role of phospholipase C in the intracellular signal control of epithelial growth was studied in normal human skin keratinocytes cultured in conditions simulating aspects of wound healing. Bacillus cereus phospholipase C decreased cell-cell contact and increased cell migration resulting in disruption of the advancing epithelial sheet. Phospholipase C-induced migration was blocked by inhibitor of the phosphoinositol signal transduction pathway neomycin sulfate and protein kinase C inhibitor RO-31-8220. Induced migration was associated with elevated levels of matrix metalloproteinase-9 which, when blocked by tissue inhibitor of metalloproteinase-1, was accompanied by a loss of migration. Adhesion studies showed that phospholipase C treatment enhanced cell binding to fibronectin, vitronectin and collagen IV. Immunostained phospholipase C-stimulated cells cultured on fibronectin showed enhanced expression and relocation of the integrin subunits alpha(v), alpha5 and beta1. Confocal microscopy showed that phospholipase C-induced levels of integrin subunit beta1 were predominantly deposited on the basal surface of the cell apparently in focal contacts and associated with actin stress fibers. These results indicate that exogenous phospholipase C signaling from a bacterial source may play an important role in perturbing normal reepithelialization via altered expression of integrins and matrix metalloproteinase-9.
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PMID:Exogenous phospholipase C stimulates epithelial cell migration and integrin expression in vitro. 1135 Jun 46

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