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)

The isolated perfused rat superior mesenteric artery preparation was used to determine whether endothelium-dependent vasodilatation occurs in this vessel, and to test whether impairment of this function may contribute to post-ischaemic mesenteric vasospasm. It was found that vessels preconstricted with noradrenaline responded to optimal concentrations of acetylcholine (3 X 10(-5) M), ADP (2 X 10(-5) M) and to isolated homologous platelets (500,000/mm3) with an 84%, 85% and 37% decrease in mean perfusion resistance, respectively. In preparations treated with collagenase to denude the vessels of endothelium there was a significantly diminished response to acetylcholine and ADP (24% & 23% decrease in resistance, respectively). Platelets, on the other hand, caused a further 34% increase in resistance. A model of mesenteric ischaemia was produced by interrupting perfusate flow through the preparation for intervals of 1 to 4 h. This was associated with morphological evidence of endothelial cell damage and with a progressive decline in the responsiveness to acetylcholine and ADP. After 1 h there was also a significant reduction in the response to platelets. With intervals of ischaemia longer than 2 h platelets caused only further constriction which could be inhibited by the serotonin antagonist, methysergide. This study suggests that an altered response of the endothelium to platelet-derived vasoactive substances may contribute to the post-ischaemic vasospasm encountered during reperfusion.
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PMID:Effect of ischaemia on endothelium-dependent vasodilatation in the isolated rat superior mesenteric artery. 334 62

Experimental factors implicated in the pathogenesis of halothane hepatotoxicity in the phenobarbital-hypoxia rat model were examined for direct effects on the energy status of isolated rat liver cells in vitro. Intact hepatocytes were isolated after collagenase perfusion of livers of adult male Fischer 344 rats previously treated with phenobarbital (0.1% in drinking water for 5-7 days) and/or deprived of food for 48 h. Cells were incubated in Krebs-Henseleit buffer + substrates for 10 min at steady states of energy metabolism, with extracellular PO2 constant at 32, 16, or 4 mmHg +/- 1% halothane. Fasting produced the largest energy deficits in incubated hepatocytes, regardless of phenobarbital treatment status, PO2 value, or presence/absence of halothane. The combination of hypoxic PO2 (4 mmHg) and 1% halothane shifted lactate metabolism toward lactate production, whereas hypoxia or halothane alone did not. Prior phenobarbital treatment plus hypoxia decreased adenosine triphosphate/adenosine diphosphate (ATP/ADP) and increased lactate production compared with drug treatment or hypoxia alone. We conclude that pathogenic factors that interact to produce halothane hepatotoxicity act directly and jointly on isolated liver cells to produce energy deficits within 10 min. Differences in the relative importance of pathogenic factors in vitro and in vivo suggest that short-term, direct effects on hepatocellular energy status are not solely responsible for halothane hepatotoxicity.
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PMID:Energy deficits in hepatocytes isolated from phenobarbital-treated or fasted rats and briefly exposed to halothane and hypoxia in vitro. 376 35

In an effort to elucidate the nature of the collagen-platelet interaction, the effects of collagen modification on platelet aggregation have been studied. We have shown that purified rat skin (salt) soluble collagen is effective at about 20 nM in mediating platelet aggregation in human platelet-rich plasma. This concentration is somewhat greater than that required of several skin insoluble collagens (ca. 10 nM). Both the alpha1(I) and alpha2 chains from rat skin soluble collagen produced platelet aggregation, but only at concentrations of about 13 muM and 55 muM, respectively. In contrast, heat-denatured collagen and chains (e.g., 65 muM alpha1(I) and 160 muM alpha2) failed to induce platelet aggregation and to inhibit platelet aggregation by native collagen. Glycopeptides were prepared from human skin insoluble collagen by extended digestion with bacterial collagenase and trypsin, and were purified by gel filtration into two classes. One class of higher molecular weight contained sialic acid, glucosamine, galactosamine, fucose, mannose, galactose, and glucose, and the other of lower molecular weight consisted primarily of a mixture of galactose and galactosyl-glucose units O-glycosidically linked to hydroxylysine-containing peptides. We found that, after the residual tryptic activity contaminating the higher molecular weight fraction was inhibited, neither of the glycopeptide classes produced nor inhibited native human skin insoluble collagen-mediated platelet aggregation at the highest concentration examined (ca. 1-2 mg glycopeptide per ml of platelet-rich plasma). Highly purified samples of the hydroxylysyl glycosides, hydroxylysylgalactose and hydroxylysylgalactosylglucose (Hyl-Gal and Hyl-Gal-Glc, respectively), were prepared from human urine and labeled at galactose using galactose oxidase followed by reduction with tritiated borohydride. Binding studies with platelet-rich plasma showed that, at concentrations greater than 50 nM, Hyl-Gal gives apparent binding to platelets, but there was no evidence of Hyl-Gal-Glc binding to platelets at concentrations up to 250 nM. At concentrations several hundredfold higher than the equivalents present in the minimum concentration of rat skin soluble collagen required for platelet aggregation, neither Hyl-Gal (at 29 muM) nor Hyl-Gal-Glc (at 18 muM) caused platelet aggregation or inhibited platelet aggregation by native collagen. Also, at a concentration of 85 muM (which represents a concentration about two thousandfold higher than the equivalents in the minimum concentration of soluble collagen required for platelet aggregation) the Gal-Glc-containing 36 residue rat skin soluble collagen alpha1(I)cyanogen bromide #5 peptide had no platelet aggregating or inhibiting activity. Modification of at least 90% of the rat skin soluble collagen carbohydrate by mild periodate oxidation had no effect on the platelet aggregating activity. Human skin insoluble collagen was reacted with periodate under the same conditions, and this had no demonstrable effect on its ability to induce platelet aggregation. This indicates that the normal carbohydrate side chains of these collagens are not required for the platelet interaction that produces the release of ADP and other metabolic constituents and leads to aggregation.Thus, collagen-platelet interactions appear to involve at least two distinct binding sites on the platelet plasma membrane. One is a protein binding site that activates platelet aggregation and has high specificity and affinity for the collagen triple-helical fold or perhaps even for a particular amino acid sequence in the triple helix.
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PMID:Collagen-mediated platelet aggregation. Effects of collagen modification involving the protein and carbohydrate moieties. 435

The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.
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PMID:Human platelet collagenase. 436 8

Membranes were obtained from Xenopus laevis oocytes after removal of follicular cells by collagenase treatment. [32P]ADP-ribosylation with pertussis toxin showed them to contain a single Mr = 40000 substrate for this toxin that co-migrates on sodium dodecylsufate-polyacrylamide gel electrophoresis with pure human erythrocyte Ni, the inhibitory regulatory component of adenylyl cyclase. [32P]ADP-ribosylation of oocyte membranes with cholera toxin also showed presence of a single substrate but of Mr = 42000. These results indicate, that the adenylyl cyclase system of oocytes, like that of somatic cells and unlike that of spermatozoids, contains the catalytic unit C and both of the known regulatory N components. The possible susceptibility to pertussis toxin of the guanine nucleotide-dependent inhibition of oocyte adenylyl cyclase by progesterone was investigated. This action of progesterone is mediated by a membrane bound receptor as opposed to a receptor of cytosolic or nuclear localization. However, the inhibitory effect of progesterone was unaffected by pertussis toxin, even though the oocyte membrane Ni was fully ADP-ribosylated with pertussis toxin, as revealed by lack of further [32P]ADP-ribosylation on subsequent re-incubation with pertussis toxin. These results indicate that the action of progesterone, in spite of being nucleotide-dependent, is either not mediated by Ni, suggesting the existence of an additional nucleotide regulatory component, or if mediated by Ni, involves a mode of regulation of this coupling protein that is different from that by which all other inhibitory hormones act on adenylyl cyclase.
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PMID:Oocyte adenylyl cyclase contains Ni, yet the guanine nucleotide-dependent inhibition by progesterone is not sensitive to pertussis toxin. 643 46

The effect on platelet function of a monoclonal platelet antibody to platelet membrane glycoprotein I was tested. This antibody, AN51, inhibited ristocetin or bovine factor VIII-induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore, the adhesion-aggregation of platelets induced by microfibrils was also inhibited by the antibody. Platelet adhesion to rabbit aorta subendothelium was impaired by the antibody. The persistent adhesion of platelets to collagenase-treated subendothelium was also inhibited. These findings strongly suggested that platelet membrane glycoprotein I could interact with a non-collagenic microfibrillar component of subendothelium. The binding of factor VIII/von Willebrand factor to platelet membrane in the presence of ristocetin was decreased in the binding site for factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium.
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PMID:Monoclonal antibody to human platelet glycoprotein I. II. Effects on human platelet function. 679 59

Basolateral membranes of microdissected collagenase-treated fragments of renal tubules from the mouse were examined using the cell-attached and the cell-free variants of the patch-clamp technique. With a K(+)-rich solution in the pipette, a highly active, inwardly rectifying K+ channel was observed on intact cells of the cortical collecting tubule (CCT). The mean inward and outward conductances were 38.5 +/- 3.1 pS and 17.3 +/- 1.8 pS, respectively (n = 4). In contrast, cell-attached patches were usually inactive when a Na(+)-rich solution filled the patch pipette. However, another type of channel with a conductance of 20-30 pS exhibited a sparse activity in 4/20 CCT. In excised, inside-out patches, the most frequent channel in CCT had an ohmic unit conductance of 27.1 +/- 1.2 pS (n = 17), excluded anions (PCl/PNa = 0.09), discriminated little between NH4+, K+ and Na+ (PNH4/PNa = 1.5; PK/PNa = 0.9), and was much less permeable to Ca2+ and Ba2+ than to Na+ (PCa/PNa = 0.09; PBa/PNa approximately 0). The cation channel was moderately voltage-dependent, showing a decreased open probability (Po) at negative voltages. It was activated by internal calcium (threshold: 1 mumol/l-0.1 mmol/l calcium), and inhibited by the adenine nucleotides ATP, ADP and AMP with half-maximal inhibition of Po at 1.2 mumol/l AMP. As in other cell models, 3',5'-dichlorodiphenylamine-2-carboxylic acid blocked channel activity when added to the internal surface of the membrane patch. Extending our study to other parts of the renal tubule, we found that the basolateral membranes of the proximal (pars recta), distal convoluted, connecting and outer medullary collecting tubules, the thin descending limb and the medullary thick ascending limb all contained a similar Ca- and ATP-sensitive cation channel. The calcium sensitivity varied from one part to another.
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PMID:A ubiquitous non-selective cation channel in the mouse renal tubule with variable sensitivity to calcium. 753 19

Regression of the rat ventral prostate occurs when the level of 5 alpha-dihydrotestosterone, the trophic hormone, drops below the threshold required to suppress apoptosis. The induction of apoptosis in the ventral prostate is accompanied by the increase in the steady-state level of a number of mRNAs coding for proteins that are involved in the latter stages of apoptosis and thus represent secondary thanatogens. These include proteases (cathepsins, plasminogen activators, and collagenase), clusterin, poly(ADP)ribose polymerase, tenascin, and several unidentified genes, as well as several RNases and the classical Ca2+,Mg(2+)-dependent endonuclease. In addition, insulin-like growth-factor-binding protein 5 (IGFBP-5) is induced de novo. We propose that IGFBP-5 may serve to trigger the apoptotic process through the attenuation of the insulin-like growth factor signalling system (which is necessary for cell survival), and as such, represents a primary thanatogen in the prostate.
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PMID:The role of growth factors in the suppression of active cell death in the prostate: an hypothesis. 754 88

The aim of the study was to investigate the effect of aging on cytoprotective properties of prostaglandins. Hepatocytes were obtained by collagenase perfusion of livers of young (4-6 mo) and old (24-28 mo) male Wistar rats. Cells were incubated for 1.5 h in Krebs-Ringer-bicarbonate buffer containing glucose and 3H-leucine in the presence of galactosamine (2.5-100 mM), PGE1, or two prostacyclin analogues: 9 beta-methylcarbacyclin and TRK-100. Cell damage was assessed by decrease in the rate of protein synthesis measured as 3H-leucine incorporation into acid precipitable material, and by increase in lactate dehydrogenase release into the medium. Hepatocytes from old rats were more susceptible to suppression of protein synthesis by GalN than cells of young ones. Preincubation of cells for 15 min with 9MC (41-560 nM) or PGE1 (10-100 nM), but not with TRK-100, before adding 10 mM GalN, led to a partial recovery of protein synthesis in both age groups. GalN increased LDH release and decreased ATP/ADP ratio to a similar extent in hepatocytes of young and old rats; both parameters were not altered by preincubation of cells with PGs. PGE1 and 9MC, but not TRK-100, elevated cyclic AMP content in hepatocytes of young but not old rats. Glucagon and forskolin similarly increased cyclic AMP content in cells of both young and old animals. These in vitro results suggest that PGE1 and some prostacyclin analogues might protect hepatocytes of both young and old rats from chemical damage, and stress the necessity for further research on cyto- and hepato-protection in the elderly.
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PMID:Prostaglandin cytoprotection of galactosamine-incubated hepatocytes isolated from young and old rats. 803 Aug 38

It is shown that ADP and DNP does not intensify the respiration rate in hepatocytes of rats obtained by means of trypsin or EDTA. The same cells obtained using collagenase, phosphorylate added ADP and increase the respiration rate after DNP addition. Acetylcholine added to the cell suspension in a dose of 5 x 4 x 10(-8) M) increases the efficiency of oxidative phosphorylation. The scheme of neurotransmitter regulation of intensity of respiration and efficiency of oxidative phosphorylation on the cell level is suggested.
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PMID:[Acetylcholine and effectiveness of oxidative phosphorylation in isolated rat hepatocytes]. 816 Mar 6


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