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)

Reinvestigation of the chemical structure of beta-amyloid peptide (A beta) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form A beta-(1-42), rather than the more soluble A beta-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, A beta was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the A beta were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of A beta-(1-42)/A beta-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular A beta contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque A beta, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of A beta associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing A beta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
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PMID:beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. 824 78

Many studies show a strong association between diabetes mellitus and risk for periodontal disease destruction. Patients with non-insulin-dependent diabetes mellitus have an increased risk of developing destructive periodontal disease. Under similar plaque conditions, adult patients with long-term, poorly controlled diabetes mellitus have more attachment and bone loss than controlled diabetic patients. Most patients with diabetes mellitus respond to conventional periodontal treatment, but in some cases the response may be related to the degree of metabolic control. Periodontal treatment may have a beneficial effect on the metabolic status of poorly controlled diabetes. Tetracycline therapy may be an effective adjunctive treatment in the management of periodontal disease in diabetic patients by blocking collagenase-dependent periodontal tissue destruction. Pyostomatitis vegetans is frequently associated with chronic inflammatory bowel disease and is a marker for the disease. Plaque control with chlorhexidine gluconate should be preceded by mechanical removal of plaque and calculus in patients with leukemia undergoing chemotherapy. A distinct gingival lesion is associated with Wegener's granulomatosis, a potentially fatal disease that, if detected early, has a favorable prognosis.
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PMID:Periodontal manifestations of systemic disease and management of patients with systemic disease. 840 43

We investigated 49 men with Peyronie's disease in a prospectively randomized placebo controlled double-blind study, comparing the effects on plaque size and penile deformity of intralesional purified clostridial collagenase and saline placebo. For the group as a whole, treatment out-performed placebo (p < 0.007). When patients were analyzed with respect to disease severity, those with lesser deformity responded more favorably to treatment. The absolute angular change in patients responding to treatment was small. No significant side effects were noted within a 3-month followup.
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PMID:Collagenase versus placebo in the treatment of Peyronie's disease: a double-blind study. 841 17

MMP-2, a secreted 72-kd metalloproteinase that specifically degrades type IV collagen as well as denatured collagens, has been implicated in smooth muscle cell migration. To evaluate the possible contribution of this enzyme to the formation and progression of the atherosclerotic lesion, the expression of MMP-2 was studied in human aortic tissue. MMP-2 was visualized in frozen sections of the aortic wall by an immunofluorescent technique with a polyclonal antibody. Expression of MMP-2 in the aortic extracts was also studied by zymography and Western blotting. Our results reveal that a greater amount of MMP-2 is present in fatty streaks and atherosclerotic plaques as compared with normal regions of the aorta. Immunoblotting analysis showed that MMP-2 was expressed in atherosclerotic plaque > fatty streak > normal aortic wall in a ratio of approximately 4:2:1. Zymograms show that both forms (activated and latent) of MMP-2 increased in the atherosclerotic plaques. The presence of macrophages, detected by an immunohistochemical technique in some areas of higher MMP-2 expression suggests that these cells are a possible source of MMP-2. We conclude that MMP-2 collagenase may have a role in the formation and progression of the atherosclerotic lesion and may be involved in clinical complications of atherosclerosis, such as fissure and rupture, leading to thrombosis.
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PMID:Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions. 854 99

The characteristics of a subset of atherosclerotic plaques that is responsible for myocardial infarction (infarctogenic plaques) are increasingly well defined. They include moderate size, a thin fibrous cap, and a large lipid pool. Fissuring of the cap leads to thrombotic occlusion and often to an acute coronary event. Physical stresses on, and proteolytic weakening of, the cap--both related to effects of hyperlipidemia on the plaque--increase the risk of fissuring. Treatment of hyperlipidemia leads to regression of experimental atherosclerosis, promotes regression and reduces progression of human coronary artery disease. The arterial changes in humans are predictive of reduced incidence of coronary events. This sequence of events may reflect gradual depletion of plaque lipids, and also a more rapid depletion of chronic inflammatory cells in the plaque cap that are the source of collagenase and other proteases. The primary objective of lipid-lowering therapy appears to be the induction of these changes in infarctogenic plaques, and vigorous treatment should be targeted on patients likely to harbor such plaques.
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PMID:Coronary heart disease prevention and the infarctogenic plaque. 868 41

Atherosclerotic plaque rupture may occur when regions of weakened extracellular matrix are subjected to increased mechanical stresses. Since collagen is a major determinant of extracellular matrix strength, enzymes that degrade collagen may play an important role in destabilizing the atherosclerotic lesion. To test the hypothesis that matrix metalloproteinase 1 (interstitial collagenase, or MMP-1), which initiates degradation of fibrillar collagens, colocalizes with increased stress in the fibrous cap of the atherosclerotic lesion, 12 unruptured human coronary lesions were studied. Finite-element analysis was used to determine the distribution of stress in the lesion, with estimates of material properties from previous measurements of human tissues. A computerized image analysis system was used to determine the distribution of immunoreactive MMP-1 within the fibrous tissue of the lesion. There was a significant correlation between immunoreactive MMP-1 and circumferential tensile stress in the fibrous cap within a given lesion (median Spearman rank correlation coefficient, .36; interquartile range, -.02 to .81; P < .02). Within a given lesion, the highest-stress region had twofold greater MMP-1 expression than the lowest-stress regions. In unruptured human atherosclerotic coronary lesions, overexpression of MMP-1 is associated with increased circumferential stress in the fibrous plaque. Degradation and weakening of the collagenous extracellular matrix at these critical high-stress regions may play a role in the pathogenesis of plaque rupture and acute ischemic syndromes.
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PMID:Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis. Implications for plaque rupture. 869 48

Specially-formulated low-dose doxycycline (LDD) regimens have been found to reduce collagenase activity in the gingival tissues and crevicular fluid (GCF) of adult periodontitis subjects in short-term studies. In the current, double-blind, placebo-controlled study, adult periodontitis patients were administered for 6 months a "cyclical" regimen of either LDD or placebo capsules; and various clinical parameters of periodontal disease severity, and both collagenase activity and degradation of the serum protein, alpha 1-PI, in the GCF were measured at different time periods. No significant differences between the LDD- and placebo-treated groups were observed for plaque index and gingival index. However, attachment levels, probing depth, and GCF collagenase activity and alpha 1-PI degradation were all beneficially and significantly (P < 0.05) affected by the drug regimen. We propose: 1) that LDD inhibits tissue destruction in the absence of either antimicrobial or significant anti-inflammatory efficacy; and 2) that long-term LDD could be a useful adjunct to instrumentation therapy in the management of the adult periodontitis patient.
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PMID:The "cyclic" regimen of low-dose doxycycline for adult periodontitis: a preliminary study. 872 9

Primary culture of rat islets of Langerhans lose glucose responsiveness and eventually die when cultured for a long period of time. In this study we evaluated the effect of matrigel, a basement membrane extract, on (i) islet cell survival, (ii) cell responsiveness following a glucose challenge, and (iii) mRNA levels for insulin, glucagon, and somatostatin. Pancreatic islets were isolated by collagenase digestion and plated in culture dishes either coated or not with a matrigel layer. Using the reverse hemolytic plaque assay, we determined the total number of insulin-secreting cells and the amount of insulin secreted by individual beta cells. After 1 h of exposure to 5 mM glucose, beta cells from 6-month-old rat islets cultured for 6 weeks on matrigel showed an equal number of insulin-secreting cells compared to freshly isolated islets cultured for only 3 days in the absence of matrigel (39.5 +/- 2.5 vs. 37.1 +/- 2.6%). Furthermore, the release of insulin by cells cultured on matrigel for 6 weeks increased in a glucose-dependent manner (p < 0.001) and showed an ED50 of 7 mM. However, the amount of insulin released per single beta cell was reduced by 40-60% (p < 0.02) compared to that released from isolated beta cells derived from a 3-day culture of islets. Finally, there was a 35-55% increase (p < 0.05) in the levels of insulin, glucagon, and somatostatin mRNAs in cells cultured for 6 weeks on matrigel. These data suggest a trophic effect of matrigel on the maintenance of normal beta-cell activity and function and may lead the way to the development of a new model for the study of pancreatic islets in long-term culture.
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PMID:Insulin release and insulin mRNA levels in rat islets of Langerhans cultured on extracellular matrix. 878 33

Previous studies have shown increased susceptibility to periodontal diseases in children with Down's syndrome (DS). The mechanisms involved in the periodontal inflammatory processes in DS are not fully understood. The present study characterized the periodontal status of 9 non-institutionalized DS children 9 to 17 years old (mean 13.6 years) relative to their age-matched systemically and periodontally healthy controls. The periodontal status was assessed by visible plaque index (VPI), gingival bleeding index (GBI), and probing depth. We also assessed, by sodium dodecyl sulphate polyacrylamide gel electrophoresis/laser densitometry and by zymography, the collagenase and gelatinase activities in the gingival crevicular fluid (GCF) and saliva samples collected from DS patients and from the controls. Eight of the nine DS children showed a periodontium comparable to that seen in healthy controls; beginning alveolar bone loss was radiographically seen in the DS patient with deep periodontal pockets. The endogenously active collagenase and total collagenase activities were slightly higher in GCF of DS children compared to healthy controls. Western blot demonstrated that GCF collagenase of DS patients was human neutrophil collagenase (MMP-8 or collagenase-2), which occurred in 75 kDa proMMP-8 and in DS patients, but not in controls, also in 65 kDa active MMP-8 form and occasionally lower 40-50 kDa MMP-8 species. Zymographic analysis revealed the presence of 120 kDa (MMP-9 complexed with neutrophil gelatinase associated lipocalin or NGAL), 92 kDa (MMP-9) and 72 kDa (MMP-2) gelatinases in DS and control GCF. Especially in DS GCF MMP-9 occurred in part in 82-85 kDa activated form. Salivary collagenase in DS was high when compared to controls but of the same MMP-8 type as in control saliva. Our findings suggest that in vivo activated MMP-8 in GCF derived from triggered PMNs and/or cytokine-induced periodontal fibroblasts may reflect periodontal tissue and alveolar bone destruction seen in the early stages of gingivitis/periodontitis associated with Down's syndrome.
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PMID:Characterization of matrix metalloproteinase (MMP-8 and -9) activities in the saliva and in gingival crevicular fluid of children with Down's syndrome. 886 13

The Porphyromonas gingivalis collagenase-specific serum immunoglobulin A (IgA), IgM, and IgG responses from 20 patients with early-onset periodontitis (EOP), 20 patients with adult periodontitis, (AP), and 20 age- and sex-matched healthy controls were examined by immunoblot analysis. A recombinant collagenase antigen used for the immunoblot analysis was produced by using the plasmid pGEX-2T, which allows the fusion between the collagenase and glutathione S-transferase. There was no significant difference in collagenase-specific IgG antibody detection between samples from the EOP, AP, and control groups. In contrast, 85% of AP and EOP sera had collagenase-specific IgA antibodies, whereas only 20% of control sera showed collagenase-specific IgA reactivity. Plaque samples from all groups were assessed by PCR with primers complementary to the collagenase-encoding gene prtC. The results indicated that 90% of AP and EOP plaque samples and 10% of control samples were positive for P. gingivalis. All patients with collagenase-specific IgA antibodies were PCR positive. The results of the study indicate a nearly complete concordance (k = 0.856) between the presence of collagenase-specific IgA antibodies and PCR detection of P. gingivalis. By using PCR as the "gold standard," the sensitivity and specificity of the IgA immunoblot test were 94.7 and 90.9%, respectively. Therefore, the recombinant collagenase is a potential candidate for use in the serodiagnosis of periodontitis.
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PMID:Serodiagnosis of Porphyromonas gingivalis infection by immunoblot analysis with recombinant collagenase. 888 Apr 90


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