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)

c-Jun, Jun-B, and Jun-D proteins bind to the TPA response element (TRE) either as homodimers or as Jun-Fos heterodimers. We demonstrate that c-Jun and Jun-B nevertheless differ markedly in their ability to activate AP-1 responsive genes. c-Jun is an efficient activator of the c-jun and collagenase promoters, which contain a single TRE; Jun-B is not. Furthermore, Jun-B inhibits activation of these promoters by c-Jun. On the other hand, like c-Jun, Jun-B is an efficient activator of constructs containing multimeric TREs. Using chimeric proteins, we show that the distinct behavior of c-Jun and Jun-B is due to differences in their activation domains. Trans-activation by Jun-B depends on cooperative interactions between adjacently bound factors, while activation by c-Jun does not require such interactions. This differential behavior greatly expands the regulatory potential of the Jun family.
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PMID:Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. 251 28

Tumour necrosis factor-alpha (TNF-alpha) is secreted by macrophages in response to inflammation, infection and cancer. Sublethal doses of recombinant TNF-alpha to rats causes cachexia, anaemia and inflammation. TNF-alpha plays a major part in tissue inflammation and remodelling by stimulating production of collagenase. Cellular responses to TNF-alpha are initiated by binding to high-affinity cell surface receptors. TNF-alpha then profoundly affects gene regulation, stimulating the fos, myc, interleukin-1 and interleukin-6 genes and inhibiting the type I collagen gene. Here we demonstrate that TNF-alpha also stimulates collagenase gene transcription; this stimulation is mediated by an element of the gene that is responsive to the transcription factor AP-1, the major component of which (jun/AP-1) is encoded by the jun gene; and that TNF-alpha stimulates prolonged activation of jun gene expression. This prolonged induction of jun contrasts with its transient activation by the phorbol ester TPA and provides a physiological example of the ability of jun/AP-1 to stimulate its own transcription. This may be a key mechanism for mediating at least some of the biological effects of TNF-alpha.
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PMID:Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. 253 68

In order to examine the involvement of protein kinase C (PKC) in the transcriptional activation of genes by TPA (12-0-tetradecanoyl phorbol 13-acetate) we have constructed a series of PKC expression plasmids. Transient expression of an active fragment of PKC in rat fibroblasts resulted in the transcriptional activation of a TRE (TPA-responsive element)-CAT chimeric gene which contains various repetitions of collagenase TREs. These provide the first direct evidence that kinase activity of PKC is involved in TPA-induced transcriptional activation through TRE.
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PMID:Direct evidence that the kinase activity of protein kinase C is involved in transcriptional activation through a TPA-responsive element. 275 29

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
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PMID:Control of gastrin release in cultured gastrinoma-derived G cells. 289 16

The promoter regions of several phorbol diester-(TPA-) inducible genes (collagenase, stromelysin, hMT IIA, and SV40) share a conserved 9 bp motif. Synthetic copies of these closely related sequences conferred TPA inducibility upon heterologous promoters. Footprinting analysis indicated that these TPA-responsive elements (TREs) are recognized by a common cellular protein: the previously described transcription factor AP-1. A point mutation that eliminated the basal and induced activity of the TRE also interfered with its ability to bind AP-1. Treatment of cultured cells with TPA led to a rapid 3- to 4-fold increase in TRE binding activity, by a posttranslational mechanism. These results strongly suggest that AP-1 is at the receiving end of a complex pathway responsible for transmitting the effects of phorbol ester tumor promoters from the plasma membrane to the transcriptional machinery.
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PMID:Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. 303 32

The enhancer-binding protein AP-1 has been purified to greater than 95% homogeneity from HeLa cells by sequence-specific DNA affinity chromatography and identified as a 47 kd polypeptide. Purified AP-1 activates transcription in vitro of the wild-type human metallothionein IIA (hMT IIA) gene but not mutant hMT IIA promoters lacking AP-1 recognition sites. DNAase I protection analysis indicates that genetically defined enhancer elements in hMT IIA, SV40, and the human collagenase gene contain high-affinity AP-1-binding sites, each with a conserved recognition motif, TGACTCA. These three genes are transcriptionally induced by treatment of cells with the tumor promoter TPA. Here we demonstrate that multiple synthetic copies of the consensus AP-1-binding site can act as TPA-inducible enhancers in various plasmid constructs after transfection into HeLa cells. These findings suggest that AP-1 is a transcription factor that functions by interacting with a specific enhancer element, and that its activities may be modulated by treatment of cells with TPA, known to stimulate protein kinase C.
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PMID:Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. 303 33

We studied PGE2-release from isolated human gastric mucosal cells. Mucosa was obtained at surgery and cells were dispersed by collagenase and pronase. Centrifugation with Percoll yielded a fraction of light density cells (70-75% parietal cells; 2-4% mast cells) revealing maximal rates of PGE2-release. A radioimmunoassay was used to measure PGE2-release into the incubation medium. Calcium ionophore A23187 which aids calcium transport across membranes caused a 3.5-fold increase of PGE2-release; this effect was abolished in calcium-free incubation medium. PGE2-release was also stimulated by phospholipase C (100 mU/ml) which is known to induce phosphoinositol breakdown, as well as by 1-oleyl-2-acetyl-sn-glycerol (OAG; 10 microM) and by 12-O-tetradecanoyl-13-acetate (TPA; 10 microM) which cause direct activation of protein kinase C without preceding induction of phosphoinositol breakdown. The response to TPA was potentiated by A23187. The calmodulin antagonist naphthalene sulfonamide W 7 reduced PGE2-release in response to A23187 and TPA (IC50: 1 microM). Our data indicate that PGE2-release of human gastric mucosal cells is stimulated by calcium influx as well as by indirect (phospholipase C) and direct (OAG, TPA) activation of protein kinase C. Stimulation of PGE2-release involves calmodulin-mediated mechanisms.
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PMID:[Calcium, phospholipase C and protein kinase C stimulate prostaglandin secretion of isolated gastric mucosa cells of the human]. 347 5

Rat pancreatic acini were prepared with collagenase A and collagenase P and their secretory response to carbachol tested. The collagenase P gave the best acinar suspension, providing that the digestion was performed in the absence of added calcium and in the presence of a low concentration of albumin. More than ninety percent of the acini prepared with this crude collagenase were viable as judged by a coloration with eosine. Their basal amylase secretion was below 3% amylase released within 20 minutes. They responded to cholecystokinin (7-fold stimulation, EC50: 10 pM), to bombesin (7-fold stimulation, EC50: 1 nM), to carbachol (7-fold stimulation, EC50: 1 microM), to fluoroaluminate (4-fold stimulation, EC50: 3 mM) or to TPA (4-fold stimulation, EC50: 100 nM). Acini preloaded with fura2 and incubated in the presence of 0.5 mM extracellular calcium were able to maintain a large (5,000-fold) gradient of calcium across their plasma membrane. Carbachol, CCK-8 and bombesin increased the intracellular calcium concentration 6-fold, within 10 seconds. This level decreased for the next 20 seconds but remained higher than the basal value for the next 10 minutes. These acini could be permeabilized with a low concentration (0.1 U/ml) of streptolysin O without affecting the basal amylase secretion, an index of the integrity of zymogen granules. It is concluded that pancreatic acini which have retained their responsiveness to major pancreatic secretagogues can be prepared with crude collagenase and permeabilized with streptolysin O. They can thus be used as a model for the study of stimulus-secretion coupling in exocrine glands.
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PMID:Isolation of rat pancreatic acini with crude collagenase and permeabilization of these acini with streptolysin O. 767 14

In order to study the cellular mechanisms involved in peptide YY (PYY) and truncated glucagon-like peptide 1 (TGLP1) release, a model of rat intestinal cells dispersed with collagenase/EDTA and enriched for L-cells by counterflow elutriation was developed. Elutriation significantly increased in the harvested cells the concentration of PYY (828 +/- 97 vs 151 +/- 16 fmol/10(6) cells) and TGLP1 (1,094 +/- 109 vs 167 +/- 20 fmol/10(6) cells), and brought the contribution of L-cells to 4-5% of the total cell population. Forskolin (1-10 microM) and dibutyryl cyclic AMP (dbcAMP, 1-5 mM) increased over an 1-h period PYY and TGLP1 secretion, with a maximal rate at 5 microM forskolin (232% and 250% of basal, respectively) and at 5 mM dbcAMP (347% and 234% of basal, respectively). Furthermore, 3-isobutylmethyl xanthine (IBMX, 1 mM) increased PYY (226% of basal) and TGLP1 (198% of basal) secretion. A combination of both 10 microM forskolin and 1 mM IBMX stimulated in an additive manner PYY (389% of basal) and TGLP1 (393% of basal) secretion. TPA (12-0-tetradecanoylphorbol-13-acetate, 0.1-1 microM) dose-dependently increased the secretion of PYY and TGLP1 (maximal release at 328% and 326%, respectively), whereas 4 alpha-phorbol was ineffective. Ionomycin (1-5 microM) and thapsigargin (0.1-5 microM) produced a dose-dependent increase in PYY and TGLP1 release (272% and 337% of basal for 5 microM ionomycin; 342% and 339% of basal for 5 microM thapsigargin, respectively). At gel chromatography, the immunoreactive PYY and TGLP1 material in cell extracts and in release medium co-eluted with the respective synthetic peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Secretion of peptide YY and truncated glucagon-like peptide 1 by isolated intestinal cells in rats]. 781 61

We have previously shown that a Long Terminal Repeat (LTR) of the Intracisternal A-type Particle (IAP) element was activated by ras oncogenes. Here we show that, like the somatostatin CRE (som CRE) and the collagenase TPA Response Element (coll TRE), the IAP CRE is activated by c-jun and that Val 12 Ha-ras cooperates with c-jun to activate these motifs. Neither jun-B nor jun-D activated the IAP CRE, although they were able to act on the som CRE and the coll TRE and to synergize with ras. The CREB factor activated both CREs and modestly inhibited the coll TRE, but diminished the effect of ras on the coll TRE. Finally, forskolin was shown to cooperate with Ha-ras to activate the CRE and the coll TRE. Taken together, these results show that CREB is not involved in ras activation of the CRE and suggest that c-jun is at least one of the elements implicated in this phenomenon.
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PMID:Differential effects of c-jun and CREB on c-AMP response element activation by Ha-ras. 790 82


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