Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leupeptin, antipain, tosyl-lysylchloromethane (Tos-Lys-CH2Cl) and benzyloxy-carbonylphenylalanylalanyldiazomethane (Z-Phe-Ala-CHN2) inhibit reversibly the resorption induced by parathyroid hormone or heparin in cultured mouse bones. Leupeptin and antipain do not affect collagenase production and activity or the enhanced secretion of beta-glucuronidase induced by the bone-resorbing agents. They might thus act by a direct (extracellular?) inhibition of lysosomal thiol proteinases.
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PMID:Inhibition of bone resorption in culture by inhibitors of thiol proteinases. 627 2

A leupeptin analogue, pyroglutamyl-Leu-Arg-CHO (Pyr-Leu-Arg-CHO), is an inhibitor of urokinase and plasmin, while leupeptin inhibits only plasmin. Pyr-Leu-Arg-CHO was shown to inhibit in vitro invasion of human fibrosarcoma HT1080 cells reducing cellular collagenase activity. Pyr-Leu-Arg-CHO suppressed the invasion of the cells in a Boyden chamber assay with an IC50 of 12 micrograms/ml. Addition of plasminogen to HT1080 cells increased the type IV collagenase activity, and Pyr-Leu-Arg-CHO inhibited this activation of the collagenase with an IC50 of 3 micrograms/ml. Leupeptin inhibited both the invasion and collagenase activation at higher concentrations than that of Pyr-Leu-Arg-CHO. The gelatin zymography of the conditioned medium revealed that a new gelatinolytic band, possibly an activated form of MMP-2, appeared by the addition of plasminogen. The activation of MMP-2 was also inhibited strongly by Pyr-Leu-Arg-CHO. These results indicate that Pyr-Leu-Arg-CHO suppresses the in vitro invasion by preventing the activation of type IV collagenase through inhibition of the urokinase-plasmin system.
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PMID:Suppression of in vitro invasion of human fibrosarcoma cells by a leupeptin analogue inhibiting the urokinase-plasmin system. 772 42

We monitored the volume of C6 glioma cells in suspension using a Coulter Counter and exposed the cells to micromolar or nanomolar levels of collagenase or clostripain. In 13 experiments, type IV collagenase (310 units ml-1; approximately 3 microM L-1) decreased the volume by 8-12%, 8 min after addition. In 13 of 21 experiments, the volume decrease was followed by a volume regulatory increase (VRI) back to control levels in the continued presence of collagenase. The shrinkage evoked by type IV collagenase was eliminated by heat-inactivation of the enzyme preparation. A highly purified collagenase (type VII) at the same concentration evoked a relatively minor decrease in volume. A well-known contaminating protease present in type IV collagenase, clostripain, which specifically cleaves arginyl peptide bonds, evoked a 7 +/- 2% shrinkage (100 nM L-1, 7 experiments). Clostripain did not evoke a volume regulatory increase. The initial velocity of shrinkage evoked by clostripain (0.0012 pL min-1, 0.0034 pL min-1, 0.0132 pL min-1; 1 pL = 10(-12) liters) scaled with its concentration (1 nM L-1, 10 nM L-1, 100 nM L-1). The effect of clostripain was inhibited by heat-inactivation of the enzyme. Leupeptin, an inhibitor of clostripain, prevented the decrease in volume evoked by clostripain. The activity of stretch-activated ion channels was unaffected by type IV collagenase. Barium, cesium, amiloride, DIDS, or bumetanide failed to block the shrinkage evoked by type IV collagenase. These results demonstrate that clostripain, present in crude collagenase enzyme preparations, causes the shrinkage, and that C6 glioma cells can undergo a volume regulatory increase at virtually constant osmotic pressure. In addition, cleavage of a cell surface moiety, which contains arginine, and possibly proline, causes shrinkage. This moiety may be part of the extracellular or intracellular matrix providing mechanical support to the cells. VRI reflect actions of another substance in the type IV crude collagenase preparations, on a receptor independent of the arg-pro moiety. The enzymatic modulation of glioma cell volume by these two receptors may reflect a new mechanism by which such cells, and possibly other glia, regulate their contact area and interactions with other cells in the central nervous system.
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PMID:Enzymatic modulation of cell volume in C6 glioma cells. 1040 29

Degradation of type I collagen by Porphyromonas gingivalis was monitored by fluorogenic, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and growth assays. All three assays showed that inactivation of both the rgpA and rgpB genes was necessary to completely eliminate the capacity of P. gingivalis to cleave type I collagen. Leupeptin, an Arg-gingipain-specific protease inhibitor, almost completely inhibited collagen degradation by P. gingivalis cells whereas cathepsin B inhibitor II, a Lys-gingipain inhibitor, did not. A purified preparation of Arg-gingipains A and B hydrolyzed gelatin but did not cleave type I collagen, suggesting that the enzymes must be attached to the cell surface to exert collagenase activity. A number of substances used as adjuncts in periodontal therapy were also tested for their capacity to inhibit collagenase activity of P. gingivalis. Tetracycline, doxycycline, and chlorhexidine strongly inhibited collagenase activity.
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PMID:The collagenase activity of Porphyromonas gingivalis is due to Arg-gingipain. 1272 24