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)

The influence of the endothelium on pulmonary venular responses to reduced oxygen tension has not been defined. To examine this question, endothelial injury was induced in small guinea pig pulmonary artery and venule segments (effective lumen radius, 174 +/- 5 and 122 +/- 2 microns, respectively) by perfusion with either a mixture of hypoxanthine (5 mM) and xanthine oxidase (0.05 U/ml) (HX/XO) or collagenase (2 mg/ml). HX/XO significantly (p less than 0.05) reduced the relaxation of precontracted pulmonary arteries by acetylcholine (ACH), bradykinin (BK), and A-23187, and the relaxations were restored by including superoxide dismutase (40 micrograms/ml) in the HX/XO solution. However, neither HX/XO nor collagenase affected vasodilation induced by ACH, BK, and A-23187 in precontracted pulmonary venules. In contrast, HX/XO significantly (p less than 0.05) augmented the sustained contraction of pulmonary venules to hypoxia (HX/XO, 3.2 +/- 1.0 mg/mm; control, 1.0 +/- 0.5 mg/mm) and anoxia (HX/XO, 35.1 +/- 6.6 mg/mm; control, 20.3 +/- 4.0 mg/mm). Collagenase also significantly (p less than 0.05) enhanced the anoxic contractions (collagenase, 36.0 +/- 3.7 mg/mm; control, 20.9 +/- 6.8 mg/mm). Superoxide dismutase (40 micrograms/ml) and catalase (323 micrograms/ml) abolished HX-XO-induced augmentation of the hypoxic and anoxic contractions of pulmonary venules. Collagenase removed 54 +/- 8% of the venular endothelium (control, 5 +/- 1%), whereas HX/XO-exposed endothelial cells contained numerous craters. Neither gossypol (5 microM) nor methylene blue (10 microM) affected pulmonary venular contractions to reduced PO2. Endothelial damage augments the PO2-dependent contractions of the pulmonary venule, and this augmentation does not appear to be due to decreased release of endothelium-derived relaxing factor.
 ...
PMID:Effect of endothelial injury on the responses of isolated guinea pig pulmonary venules to reduced oxygen tension. 254 70

Polymorphonuclear leukocytes (PMN) accumulating at inflammatory sites have the potential to degrade collagen by releasing the metalloproteinase collagenase (EC 3.4.24.7), which is stored within the specific granules of these cells in a latent, inactive, form. In order to elucidate the activation mechanism the latent enzyme (molecular weight 91,000) was purified from human PMN and incubated with the oxygen radical-generating system of xanthine oxidase (EC 1.1.3.22) and hypoxanthine. This coincubation resulted in the activation of the latent enzyme as assessed by the collagenolytic attack on human and bovine cartilaginous tissue. Two parameters for collagenolysis were used: loss of hydroxyproline-containing fragments, and mechanical measurements reflecting the stability of tissue specimens. Superoxide dismutase (EC 1.15.1.1) as well as catalase (EC 1.11.1.6) were capable of inhibiting the activation of latent PMN collagenase by the oxygen radical-generating system. The results indicate the hydroxyl radical to be the final oxidant responsible for the activation of latent PMN collagenase. Thus a new activation mechanism of latent collagenase is presented in this paper and discussed together with the potential relevance in pathophysiologic states of acute and chronic inflammation.
 ...
PMID:Activation of latent collagenase from polymorphonuclear leukocytes by oxygen radicals. 303 4

Vascular relaxation in rabbit aortic preparations induced by acetylcholine is endothelium-dependent. The nature of the endothelium-derived relaxing factor (EDRF) has not been ascertained because it is very labile (reported half-life 6-50 seconds). To obtain a stable source of EDRF, a system was developed in which the relaxing factor was continuously produced by freshly harvested porcine endothelial cells. Endothelial cells were collected from aortas by exposing the endothelial lining to collagenase 0.1%. Cells were washed and concentrated by repeated centrifugation to obtain a high cell count (7.2 X 10(6) cells/ml). Endothelium-deprived aortic strips from rabbits were incubated in these cells suspended in tissue culture medium and fetal calf serum. The strips were precontracted with histamine. Acetylcholine was added to induce EDRF release. Significant relaxation of endothelium-deprived aortic strips was observed. Superoxide dismutase, an enzyme known to protect EDRF against inactivation, caused further relaxation, which was inhibited by the addition of hemoglobin, an agent known to inhibit the relaxing action of EDRF. Even without the addition of acetylcholine, hemoglobin caused contraction of the denuded aortic strips in suspension of porcine endothelial cells, demonstrating spontaneous EDRF release. Hemoglobin had no effect in cell-free medium. Endothelial-cell-dependent relaxation occurred without attachment of endothelial cells to the endothelium-deprived aortic strips: when the cell suspension was replaced by cell-free medium, relaxation did not occur after acetylcholine. Scanning electron microscopy showed no attachment of endothelial cells to the subendothelial layer. It can be concluded that freshly harvested endothelial cells produce endothelium-derived relaxing factor with an without stimulation by acetylcholine.
 ...
PMID:Release of endothelium-derived relaxing factor from freshly harvested porcine endothelial cells. 349 57

We examined whether the generation of reactive oxygen metabolites (as quantified by measuring luminol-amplified chemiluminescence) by isolated rat glomeruli could be triggered enzymatically. No response was observed with thrombin (1 or 10 U/ml), collagenase (100, 200, or 400 U/ml), or plasmin (0.1 or 1 U/ml). In contrast, chymotrypsin and trypsin caused a dose-dependent (10-200 micrograms/ml) increase in chemiluminescence from glomeruli. The peak response with chymotrypsin (100 micrograms/ml) and trypsin (50 micrograms/ml) was as follows: resting, 16 +/- 2 X 10(3) cpm/mg protein, n = 17; chymotrypsin, 233 +/- 58 X 10(3) cpm/mg protein, n = 17; and trypsin, 221 +/- 38 X 10(3) cpm/mg protein, n = 10. Tubules had only a minor response. Soybean trypsin inhibitor and aprotinin caused marked inhibition, indicating the dependency of the chemiluminescence response on the protease enzyme activity. The chemiluminescence response was by glomeruli rather than by "contaminating" leukocytes, since a similar marked response (n = 6) was observed in glomeruli isolated from cyclophosphamide-treated leukopenic (leukocyte less than 1,000/mm3) rats. Superoxide dismutase, a scavenger of superoxide, and free-radical scavengers benzoate and tryptophan inhibited the glomerular chemiluminescence response to trypsin and chymotrypsin. Neutral proteases from infiltrating leukocytes and/or renal tissue have been shown to be released in glomerular diseases; our results, which show the generation of chemiluminescence in response to neutral proteases, suggest a potential mechanism for the production of reactive oxygen metabolites in glomerular diseases.
 ...
PMID:Trypsin- and chymotrypsin-induced chemiluminescence by isolated rat glomeruli. 359 31

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1 beta-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.
 ...
PMID:Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. 784 4

In order to study decidual proteins produced during pregnancy, decidual cells were isolated from term placental membranes by collagenase digestion and Percoll gradient centrifugation. Serum-free CMRL-1066 medium, conditioned for 148 h with the purified decidual cells, was collected and concentrated by ultrafiltration and applied to a Sephadex G-50 column. The protein-containing fractions from the column were concentrated, dialyzed, lyophilized, applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transferred to a polyvinylidene difluoride membrane, followed by sequencing. Superoxide dismutase and two new members of the decidual protein family, beta 2-microglobulin precursor and ubiquitin, were identified by 100% N-terminal sequence homology, and similarities of molecular weights and residue contents.
 ...
PMID:Production of superoxide dismutase, beta 2-microglobulin and ubiquitin by human term decidua in vitro. 936 43