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)

Entamoeba histolytica cells secrete electron-dense granules (EDGs) that have collagenase activity. To study the possible involvement of calmodulin (CaM) on EDG secretion, the effect of several CaM antagonists (TFP, R24571, W-7, W-5, dibucaine and DL-propranolol) was tested on this cellular function. Except for W-5 and dibucaine, the rest of these compounds inhibited EDG secretion. Transmission electron microscopy of collagen-activated trophozoites showed numerous EDGs located in or near the surface membrane. In contrast, trophozoites incubated with TFP showed no EDGs. Protein kinase C inhibitors (H-7, ML-9) had no effect on EDG secretion, suggesting that CaM antagonists acted by selectively inhibiting CaM. These results suggest that a CaM-dependent process is involved in EDG secretion.
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PMID:Possible role of calmodulin in the secretion of Entamoeba histolytica electron-dense granules containing collagenase. 165 40

The involvement of cAMP- and calcium-dependent pathways on the inhibitory effect of CsA (0.5 micrograms/ml) on insulin and glucagon release was studied in collagenase-isolated islets. CsA suppressed by 50% the release of insulin in pertussis toxin treated islets stimulated by 20 mM D-glucose. CsA blocked glucagon and insulin release induced by 0.2 mM IBMX (80% and 50% respectively). Similarly it inhibited glucagon and insulin release induced by 1 microM A23187 (53% and 40% respectively). CsA also abolished 0.1 microM glucagon-induced insulin release and 10 ng/ml VIP-induced glucagon release (70% and 38% respectively). The glucagon response to 2 mM D-glucose and to 10 mM arginine was decreased 25% and 45% respectively by CsA. The inhibitory effect of 0.1 microM somatostatin on insulin release was significantly abolished by CsA (p less than 0.001 vs control). On the other hand 1 microM forskolin induced insulin and glucagon release was not modified by CsA. Rats treated with CsA (10 mg/kg body wt) during 10 days showed hyperglycaemia, hypoglucagonemia and higher contents of pancreatic glucagon. It is concluded that CsA affects alpha- and beta-cell function, in vivo and in vitro, acting through calcium and cAMP-dependent pathways. This latter pathway involves the Ca(2+)-calmodulin dependent phosphodiesterase and the regulatory proteins Gs and Gi.
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PMID:Mechanisms of action of cyclosporin A on islet alpha- and beta-cells. Effects on cAMP- and calcium-dependent pathways. 166 May 57

Chondrocyte metalloproteinases appear to play a major role in the development of osteoarthritis. The intracellular post-traductional mechanisms regulating collagenase and proteoglycanase are not known. Calmodulin antagonists including phenothiazine and sulfonamide derivatives significantly increased proteoglycanase activity and decreased collagenase activity. H-7, a specific inhibitor of protein kinase C, had no effect on the two metalloproteinase activities, and calmodulin was ineffective in in vitro assays upon metalloproteinase activities. We postulate that collagenase and proteoglycanase activities are controlled by calmodulin-dependent regulation.
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PMID:Calmodulin-dependent collagenase and proteoglycanase activities in chondrocytes from human osteoarthritic cartilage. 184 28

The present studies were conducted to further evaluate inositol phosphate formation and metabolism in prostaglandin F2 alpha (PGF2 alpha)-stimulated bovine luteal cells. Corpora lutea were dispersed with collagenase, and luteal cells were prelabeled for 3 h with [3H]inositol. Inositol phosphates produced in response to PGF2 alpha were analyzed by ion exchange column chromatography and HPLC. Time-course experiments revealed that significant increases in inositol trisphosphate (InsP3) were apparent within 5 sec of incubation with PGF2 alpha. Increases in inositol bisphosphate (InsP2) were also apparent within 5 sec. InsP1 and InsP4 were observed after a short (5-sec) lag period. HPLC revealed that PGF2 alpha provoked rapid (5 sec) increases in inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), which was rapidly converted to inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5-P4) and inositol 1,3,4-trisphosphate (Ins 1,3,4-P3). The primary inositol bisphosphate isomer present in PGF2 alpha-stimulated bovine luteal cells was inositol 1,4-bisphosphate (Ins 1,4-P2), with lesser amounts of Ins 1,3-P2. Inositol monophosphates were also increased. These findings were confirmed in studies in which the metabolism of purified [3H]Ins 1,4,5-P3 was followed temporally in saponin-permeabilized bovine luteal cells. Additional studies demonstrated the presence of an enzyme, InsP3-3-kinase, in the cytosolic fraction of bovine corpora lutea. InsP3-3-kinase phosphorylated Ins 1,4,5-P3 to form Ins 1,3,4,5-P4. The activity of InsP3-3-kinase was calcium dependent and was enhanced by calmodulin at low calcium concentrations. Calmidazolium, a calmodulin inhibitor, reduced InsP3-3-kinase activity in a concentration-dependent manner. These results demonstrate the presence of multiple polyphosphorylated inositol phosphates in PGF2 alpha-stimulated bovine luteal cells. The isomers were formed via the action of a specific calcium/calmodulin-regulated kinase (InsP3-3-kinase), which phosphorylated Ins 1,4,5-P3 during agonist-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate. These data suggest that the inositol tris/tetrakisphosphate pathway is an important sequelae to PGF2 alpha-stimulated inositol phospholipid hydrolysis, and that the pathway may be activated during agonist-mediated calcium mobilization.
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PMID:Prostaglandin F2 alpha stimulates inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate formation in bovine luteal cells. 184 60

The aim of this work was the identification of the calmodulin-stimulated protein phosphatase, calcineurin, in rat pancreatic islets. For this purpose, a high-affinity calcineurin antibody and the Western blotting technique were used to detect the presence of calcineurin in freshly collagenase-isolated islets. The calcineurin content detected by this method was about 0.30 ng islet (approx. 0.07% of the total islet protein). The subunit composition and Mr of islet calcineurin were similar to those of bovine brain calcineurin. Incubation of nitrocellulose membranes of the Western blotting, containing the islet protein fractions, with 125I-labeled calmodulin and 45Ca2+ demonstrated that the A subunit bound calmodulin, while the B subunit bound Ca2+. The presence of calcineurin in the islets of Langerhans would suggest its possible participation, as a counterpart of the kinases effect, in the regulatory mechanism of insulin secretion.
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PMID:Identification of the calmodulin-regulated protein phosphatase, calcineurin, in rat pancreatic islets. 184 10

Parietal cells are a major source of gastric mucosal prostaglandins in various species. We examined cholinergic stimulation of prostaglandin E2 (PGE2) release from human parietal cells; using activators of the protein kinase C we attempted to get an indirect insight into cellular mechanisms which control PGE2 release. Gastric mucosal specimens were obtained at surgery and the cells were dispersed by collagenase and pronase E. Parietal cells were enriched to 65-80% by a Percoll gradient, and were incubated for 30 min. PGE2 release into the medium (radioimmunoassay) was 74-126 pg/10(6) cells/30 min under basal conditions and was 2.6-fold increased by carbachol (10(-5) and 10(-4) M). Similarly, PGE2 release was stimulated by phospholipase C (20-200 mU/ml, 364% above basal), 1-oleoyl-2-acetyl-sn-glycerol (10(-9)-10(-5) M, 229%), 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-9)-10(-5) M, 283%) and calcium ionophore A23187 (10(-7)-10(-5) M, 219%). Simultaneous presence of A23187 and TPA synergistically induced stimulation which was slightly higher than the sum of the individual responses. N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide W-7, a putative calmodulin antagonist, inhibited TPA-induced PGE2 release at concentrations regarded specific for blocking calmodulin (IC50 = 1.5 X 0(-6) M). We conclude that in human parietal cells PGE2 is released upon cholinergic stimulation and that phospholipase C and protein kinase C are involved in the control of PGE2 release. We speculate that calmodulin might interact with a protein phosphorylated by protein kinase C to cause PGE2 release.
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PMID:Potential mediation of prostaglandin E2 release from isolated human parietal cells by protein kinase C. 222 20

Interleukin 1 (IL-1) stimulates the synthesis of collagenase in human uterine cervical fibroblasts. This inductive effect of IL-1 on collagenase production was augmented by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a specific inhibitor of calmodulin, in a dose-dependent manner. The apparent collagenase activity observed in the culture medium of the cells treated with IL-1 and 40 microM W-7 was about three times higher than that produced by the cells treated with IL-1 alone. The immunoblotting with the specific antibody against human collagenase showed that the increased collagenase activity resulted from the accelerated biosynthesis of collagenase. Another calmodulin inhibitor, trifluoperazine, enhanced the effect of IL-1 on collagenase production similarly. However, the effect of N-(6-aminohexyl)-1-naphthalenesulfonamide, the weakest inhibitor of calmodulin, was negligible. These results suggest that W-7 enhances the collagenase production by specifically inhibiting calmodulin and that calmodulin may act as a suppressor of the IL-1-induced collagenase production in human uterine cervical fibroblasts.
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PMID:Calmodulin regulates the interleukin 1-induced procollagenase production in human uterine cervical fibroblasts. 253 48

Cellular calcium homeostasis and calcium-mediated cell functions are conceptually attractive processes to be involved in the manifestation(s) of lead toxicity including impaired skeletal growth and cardiovascular and neurological dysfunction. Knowledge of Ca:Pb and Pb:Ca ratios in different structural and functional compartments of cells is essential for identifying, characterizing, and understanding the significance of Pb2+-Ca2+ interactions. Experiments were conducted to characterize the steady-state kinetic distribution and behavior of 45Ca in primary cultures of murine osteoclastic bone cells. Bone cells, derived from mouse calvaria, were enriched for osteoclasts by a sequential collagenase digestion and maintained in primary culture for 1 week. Cultures were labeled with 45Ca for two or 24 hr and the kinetic parameters were obtained by analysis of 45Ca washout curves. Cellular metabolism was based upon a model with three kinetic pools of intracellular Ca2+ containing approximately 45, 25, and 30% of the total cell calcium. In addition, we describe quantitative measurements of Ca:Pb and Pb:Ca ratios at important functional cell sites of Ca2+ transport and storage in intact cells. The intracellular relationships of Ca2+ and Pb2+ were calculated concurrently in individual cultures, using kinetic analysis of dual-label 45Ca and 203Pb washout curves. The Ca:Pb ratios of the rate constants and half-times were approximately 1:1, supporting the concept of similar cellular metabolism of the two elements. The Ca:Pb ratios for the kinetic pools and fluxes were considerably higher than 1:1. These in situ Ca:Pb relationships should be useful for designing and evaluating Ca-Pb studies with calmodulin, isolated mitochondria, and other individual components of the calcium messenger system. Moreover, these data demonstrate both similarities and differences in the kinetic distribution and behavior of Ca2+ and Pb2+ in osteoclastic bone cells.
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PMID:Quantitative interactions between Pb2+ and Ca2+ homeostasis in cultured osteoclastic bone cells. 271 79

The effect of Ca2+ ion concentration on the 25 hydroxylation of tritiated cholecalciferol (3HD3) was investigated using homogenates of ovine liver from vitamin D replete sheep. A significant decrease in the production of 25 hydroxycholecalciferol (25OHD3) was observed when the concentration of Ca2+ in the homogenate was raised above 0.68 mmol/l by the addition of calcium gluconate. Similarly, a final concentration of 37 mumol EGTA/1 (equivalent to a Ca2+ concentration of 26.5 nmol/l) was associated with a 50% reduction of 25OHD3 production. That is, a broad bell-shaped relationship was observed between the production of 25OHD3 and the Ca2+ concentration in the homogenate. These changes in the rate of production of 25OHD3 were reproduced with hepatocytes from vitamin D replete rats, prepared by collagenase perfusion, using the drugs dantrolene sodium (DaNa) to reduce (ED50 = 57 mmol/l) and veratridine to increase (ED50 = 550 mmol/l) the intracellular Ca2+ concentration. Hepatocytes from vitamin D replete rats also showed a reduction in 25 hydroxylation of D3 (ED50 = 6 ng/ml) in response to the addition of 1-25 dihydroxycholecalciferol (1-25 (OH)2D3). The calmodulin antagonists; W7, compound 48/80, trifluoperazine (TFP) and calmidazolium (R24571) were all found to effect a dose response inhibition of the 25 hydroxylation of cholecalciferol by homogenates of ovine liver. R24571 had a similar inhibitory effect (ED50 = 70 mumol/l) upon the 25 hydroxylase enzyme of rat hepatocytes. It is concluded that the 25 hydroxylation of cholecalciferol in liver of vitamin D replete rats and sheep is calcium sensitive and is reduced in the presence of increased concentrations of 1,25(OH)2D3. Calmodulin may also be involved in the regulation of hepatocyte 25-hydroxylase activity by Ca2+.
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PMID:The involvement of intracellular calcium ion concentration and calmodulin in the 25-hydroxylation of cholecalciferol in ovine and rat liver. 282 May 80

Macrophages and monocytes secrete a factor(s) which can stimulate the synthesis of collagenase in synovial cells and in chondrocytes. Incubation of rabbit chondrocytes with macrophage conditioned medium (MCM) and with the calcium channel blockers, nifedipine, verapamil or diltiazem (up to 200 microM) had no effect on collagenase synthesis. However, TMB-8 (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), an inhibitor of internal calcium movement, did inhibit the process with an IC50 of approximately 130 microM. The calmodulin antagonists, trifluoperazine, chlorpromazine and calmidazolium (R-24571) were effective inhibitors of the process with IC50's of 40 microM, 18 microM and 3.5 microM, respectively. Collagenase activity itself was not affected by these agents. The data suggests that calmodulin and/or internal calcium movement may play a role in the macrophage factor-stimulated synthesis of collagenase in rabbit chondrocytes.
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PMID:The effect of calcium channel blockers and calmodulin inhibitors on the macrophage factor-stimulated synthesis of collagenase by rabbit chondrocytes. 284 10


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