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 deposition of alpha-1-antitrypsin and alpha-2-macroglobulin, both known to be inhibitors of human skin collagenase, is significantly increased in keloids and in hypertrophic scars (as compared to normal skin). However, following intralesional triamcinolone treatment, a marked resorption of these abnormal scars occurs along with a significant reduction of the alpha-1-antitrypsin deposits. These findings suggest that alpha-globulins are involved in abnormal scar formation, and that triamcinolone may remove collagenase and/or protease inhibitors--thereby allowing activation of the collagenase with subsequent breakdown and resorption of the excessive collagen.
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PMID:Tissue alpha-globulins in keloid formation. 6 77

Hydrolytic activity of various lysosomal proteases--elastase, collagenase, and cathepsins B and H--were measured in 125 middle ear effusions from patients with chronic (serous and mucoid) and acute otitis media with effusion (OME). The levels of cathepsin B activity and alpha-2-macroglobulin during the course of clinical therapies (myringotomy and tympanostomy tubing) were analyzed in 10 chronic OME cases where follow-up evaluation was possible. It is found that the level of lysosomal protease activity (elastase, collagenase and cathepsin B) was higher in acute OME than that in chronic OME; the hydrolytic activity of cathepsin B in middle ear effusions could be used as an indicator to reflect the level of lysosomal proteases activity in the middle ear; in chronic OME, inflammatory reaction including lysosomal protease activity of the middle ear mucosa at the time of the first myringotomy appeared to be more active than that at the time of the final myringotomy, but less than that in acute OME; and the proteolytic damage of lysosomal thiol proteases to the middle ear mucosa, which may be related to the chronicity of OME, could be reduced by both therapeutic myringotomy and tympanostomy.
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PMID:Kinetics of lysosomal protease activity in human otitis media with effusion. 244 31

The distribution of interstitial collagenase in a rat mammary carcinoma model system has been studied by immunocytochemistry. Rabbit antibodies were raised against collagenase from neoplastic epithelial cells which were derived from an anaplastic, invasive, rat mammary carcinoma (BC1). Specificity of the antibodies was determined by Western blot analysis which showed reactivity with the inactive procollagenase from conditioned culture medium of BC1 cells as well as with purified, active BC1 collagenase. Anti-BC1 collagenase antibodies did not recognize BC1 collagenase entrapped by the inhibitor, rat alpha-2-macroglobulin (alpha 2M), or collagenase derived from TPA-stimulated human fibroblasts. Anti-human fibroblast collagenase antibodies did not recognize BC1 collagenase, suggesting that the human-mesenchymal and rat-epithelial enzymes are immunologically distinct molecules. Collagenase was immunolocalized intracellularly in BC1 cells cultured in the presence of monensin. Neither BC1 collagenase, alpha 2M nor enzyme-inhibitor complexes were demonstrated in or around invading tumours by immunostaining of tissue sections of rat mammary carcinomas.
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PMID:Immunolocalization of collagenase in neoplastic epithelial cells. 248 53

In dust-induced, fibrosing lung processes macrophages are increased activated by foreign body reactions. The release of monokines and proteolytic enzymes, which depends on phagocytosis, may lead to destruction of the extracellular matrix with the consequence of degradation and restitution. Also the transcellular signaling or cell-matrix-interaction may finally result in development of fibrosis. However the proteolytic effect of elastase and collagenase can be inhibited by alpha-2-macroglobulin. Alpha-2-macroglobulin is a protease-inhibitor, which is synthesized by macrophages and has a wide spectrum of inhibitory abilities. Our interest was focused on observation of the production of alpha-2-macroglobulin by alveolar macrophages after stimulation with inorganic dusts of different chemical and physical properties. Rat alveolar macrophages were isolated by bronchoalveolar lavage and exposed to crocidolite, quarz or welder steam dust in vitro. The expression and secretion of alpha-2-macroglobulin was examined by non radioactive in situ hybridization, indirect immunofluorescence and radial immunodiffusion according to Mancini. The stimulated rat alveolar macrophages showed an increased expression of alpha-2-macroglobulin-mRNA and also an enhanced synthesis of alpha-2-macroglobulin-protein. Besides only small differences between the substances used for stimulation were demonstrated.
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PMID:[Expression and secretion of alpha-2-macroglobulin by dust-stimulated alveolar macrophages]. 751 74

The thinning of the cornea that occurs in keratoconus has been well described; however, the mechanism of tissue degradation remains unknown. Elevated proteinase activity is one possibility and approximately 20 publications over the last 20 years have addressed this hypothesis. Early studies reported increased collagenase and gelatinase activities in the medium of keratoconus corneal cultures. After the characterization of the matrix metalloproteinase (MMP) enzymes, studies focused on the expression of specific MMPs, in particular the gelatinases, MMP-2 and MMP-9. Matrix metalloproteinase-2 was found to be the major MMP of the cornea and was constitutively produced in normal tissue, whereas MMP-9 expression was induced by various stimuli, including phorbol esters and even tissue culturing. These studies suggested that there were no differences in the amounts or states of activation of MMP between normal and keratoconus corneas, although the amounts of some proteinase inhibitors, including tissue inhibitors of metalloproteinases, alpha-1-proteinase inhibitor and alpha-2-macroglobulin, were decreased in keratoconus. Most recently, the lysosomal proteinases, cathepsin B and cathepsin G were reported to be elevated in keratoconus corneas, and it is possible that it was cathepsin activity, not MMP activity, that was measured in some early studies. Nevertheless, there are now about 20 human MMPs identified and it is possible that some of these, other than the well known collagenase (MMP-1) and gelatinases (MMP-2 and MMP-9), could be implicated in the pathology of keratoconus. Studies have begun to address more recently described MMPs and it has been reported that the membrane-bound MT1-MMP (MMP-14), which activates latent MMP-2, was found to have increased expression in keratoconus corneas, whereas the stromelysins, MMP-3 and MMP-10, were not.
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PMID:Is the corneal degradation in keratoconus caused by matrix-metalloproteinases? 1177

Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors' profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target, antihypertensive drugs that down-regulate MMPs may offer advantages in the management of this disease.
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PMID:Consistent alterations of circulating matrix metalloproteinases levels in untreated hypertensives and in spontaneously hypertensive rats: a relevant pharmacological target. 2140 87