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)

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen-associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.
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PMID:Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats. 897 Oct 88

The present report concerns a patient who had undergone nearly total pancreatectomy (95%) with pancreatic islet autotransplantation for intractable pain caused by obstructive chronic pancreatitis. Islets were prepared by a modified collagenase digestion and were cultured in vitro in Eagel's medium in 5% CO2 in air at 37 degrees C for 5 days. The resultant preparation, containing about 150,000 islets, was injected into the recipient's liver via the umbilical vein. No complication occurred from the pancreatectomy or transplant. Postoperatively, the patient had complete relief of the abdominal pain, and the insulin-independent condition remained with normal fasting blood glucose, and hemoglobin A1c for 11 months. Subsequently the fasting hyperglycemia was evident, and the patient began oral antidiabetic medication, but 2 year after transplantation the insulin-dependent condition demanded exogenous insulin (24 U). At present the fasting serum C-peptide level is 0.6 ng/ml and the HbA1c of 5.8% confirms the normoglycemic condition at the same insulin dose. Islet auto-transplantation should be considered as an adjunct procedure to prevent or ameliorate diabetes after total or nearly total pancreatic resection.
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PMID:[Management of diabetes induced by nearly total (95%) pancreatectomy with autologous transplantation of Langerhans cells]. 928 Aug 85

We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination (baseline) and on three separate occasions during a 48-month follow-up period. All patients had normal urinary albumin excretion (<20 microg/min) at the first three examinations. At the fourth examination (48 months after the first examination), 22 patients had normal urinary albumin excretion and eight had microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min). Compared with patients with normal urinary albumin excretion, patients with microalbuminuria had significantly higher plasma levels of MMP-9 at the second (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14 microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01) examinations, but not at the first examination (34+/-12 microg/L v 33+/-14 microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the occurrence of microalbuminuria within 4 years. The groups did not differ with regard to age, sex, duration of NIDDM, blood pressure, or mean glycated hemoglobin. In addition, the eight patients with microalbuminuria were treated with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily) for 6 months. Microalbuminuria was reduced to within the normal range, and plasma MMP-9 concentrations were significantly decreased with the cilazapril treatment (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1 showed no change during the study period. These data suggest that plasma MMP-9 concentrations preceded and may predict the development of microalbuminuria in NIDDM.
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PMID:Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus. 977 33

The present report demonstrates that the Gymnorhynchus gigas plerocercoid possesses various types of endo- and exoproteases with activity against general (azocoll, azocasein, and azoalbumin) and specific substrates (elastin, keratin, collagen, hemoglobin, fibrinogen, plasma, and immunoglobulin G). The activity against collagen is principally due to a 24-kDa collagenase with an isoelectric point of 7.5 and without isoforms or sugar residues. Moreover, its high degree of proteolytic activity against collagen under conditions similars to those encountered by the parasite in its hosts (pH and temperature) and its similarity to metallo- and cysteine proteases (the principal protease types implicated in degradation of tissues) suggests the importance of this molecule as a lytic enzyme principally implicated in penetration processes across the teleost muscle or/and into the gastrointestinal system of elasmobranch fishes as well as in molting processes.
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PMID:Proteolytic activity of the Gymnorhynchus gigas plerocercoid: purification and properties of a collagenase from the crude extract. 995 Feb 30

Collagenous proteins are especially prone to nonenzymatic glycation, because they contain several dibasic amino acid residues with free amino groups, have a very slow turnover rate, and are exposed to ambient levels of glucose. The aim of this study was to determine the time-dependent course of advanced glycation process in diabetic rats in relation to glycemic control and duration of diabetes, compared to age-matched controls. Immunochemical assay with antibodies to advanced glycation end products (AGE) was first developed to qualitatively detect and quantify the AGE formed in rat tendon and aortic collagen. Individual collagen samples were extracted by extensive pepsin and collagenase digestion. The amount of AGE was measured by competitive ELISA and results were expressed as AGE U/mg collagen. Diabetic rats showed a significant increase in AGE content in aortic collagen at 20 weeks (n = 6, 206.6 +/- 16.7 U/mg collagen) compared with that measured at 4 and 12 weeks (n = 6, 110 +/- 12.8 U/mg collagen, and n = 13, 184.9 +/- 12.3 U/mg collagen at 4 and 12 weeks, respectively; p < 0.001 between 20 weeks and 4 weeks; p < 0.01 between 20 weeks and 12 weeks). The amount of AGE in tendon collagen of diabetic rats increased from 1.9 +/- 0.38 U/mg at 4 weeks to 11.2 +/- 6.1 U/mg collagen at 20 weeks, p < 0.001. Considerable disparity was observed in the intensity of glycation between aortic and tendon collagen. AGE-content per mg of aortic collagen was several-fold to that found in tendon collagen (p < 0.001). To investigate the effect of glycemic control on the advanced glycation process, total aortic AGE-collagen content was compared between untreated diabetic rats (D; n = 13, 184.9 +/- 12.3 U/mg) and diabetic rats treated for 12 weeks with insulin (DI; n = 6, 133.9 +/- 10.7 U/mg), or phlorizin (DP; n = 6, 132.4 +/- 8.9 U/mg), or by a combination of insulin/phlorizin (DIP; n = 6, 124.3 +/- 6.5 U/mg). In spite of therapy used, all groups of diabetic animals had a significantly higher aortic AGE-collagen content than those in the nondiabetic control group (C: n = 8, 104.6 +/- 14.9 U/mg) of the same age (D, DI, DP, DIP vs. C, p < 0.001). Comparison between the mean levels of glycated hemoglobin (D: 5.62 +/- 0.38 % vs. C: 1.7 +/- 0.05%) and mean AGE levels in the studied group of animals yielded a very good exponential correlation (r = 0.89, p < 0.001). Glycation-derived late-stage collagen modification was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and by immunoblotting confirmed to contain (an) AGE-structure(s). Our study provides strong immunochemical evidence of AGE formation in vivo during hyperglycemia, and of their temporal association with structural alterations of extracellular matrix proteins. The advanced glycation process is retarded and reduced in intensity, but not completely abolished, by glycemia regulation with, or independently of, insulin.
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PMID:Rat tissue collagen modified by advanced glycation: correlation with duration of diabetes and glycemic control. 1053 30

The genetic structure and evolution of a novel exchangeable meningococcal genomic island was defined for the important human pathogen Neisseria meningitidis. In 125 meningococcal strains tested, one of three unrelated nucleotide sequences, designated exl (exchangeable locus), was found between a gene required for heme utilization, hemO, and col, encoding a putative Escherichia coli collagenase homologue. The 5' boundary of each exl cassette was the stop codon of hemO, whereas the 3' boundary was delineated by a 33-bp repeat containing neisserial uptake sequences located downstream of col. One of the three alternative exl cassettes contained the meningococcal hemoglobin receptor gene, hmbR (exl3). In other meningococcal strains, hmbR was absent from the genome and was replaced by either a nucleotide sequence containing a novel open reading frame, exl2, or a cassette containing exl3. The proteins encoded by exl2 and exl3 had no significant amino acid homology to HmbR but contained six motifs that are also present in the lipoprotein components of the lactoferrin (LbpB), transferrin (TbpB), and hemoglobin-haptoglobin (HpuA) uptake systems. To determine the evolutionary relationships among meningococci carrying hmbR, exl2, or exl3, isolates representing 92 electrophoretic types were examined. hmbR was found throughout the population structure of N. meningitidis (genetic distance, >0.425), whereas exl2 and exl3 were found in clonal groups at genetic distances of <0.2. The commensal neisserial species were identified as reservoirs for all of the exl cassettes found in meningococci. The structure of these cassettes and their correlation with clonal groups emphasize the extensive gene pool and frequent horizontal DNA transfer events that contribute to the evolution and virulence of N. meningitidis.
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PMID:exl, an exchangeable genetic island in Neisseria meningitidis. 1117 44

The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.
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PMID:Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model. 1271 30

Prolonged hypothermia reduces ischemic brain injury, but its efficacy after intracerebral hemorrhagic (ICH) stroke is unresolved. Rats were implanted with core temperature telemetry probes and subsequently subjected to an ICH, which was produced by infusing bacterial collagenase into the striatum. Animals were kept normothermic (NORMO), or were made mildly hypothermic (33-35 degrees C) for over 2 days starting 1 hour (HYP-1), 6 hours (HYP-6), or 12 hours (HYP-12) after collagenase infusion. Others were cooled for 7 hours beginning 1 hour after infusion (BRIEF). Skilled reaching, walking, and spontaneous forelimb use were assessed. Normothermic ICH rats sustained, on average, a 36.9-mm3 loss of tissue at 1 month. Only the HYP-12 group had a significantly smaller lesion (25.5 mm3). Some functional improvements were found with this and other hypothermia treatments. Cerebral edema was observed in NORMO rats, and was not lessened significantly by hypothermia (HYP-12). Blood pressure measurements, as determined by telemetry, in BRIEF rats showed that hypothermia increased blood pressure. This BRIEF treatment also resulted in significantly more bleeding at 12 hours after ICH (79.2 microL) versus NORMO-treated rats (58.4 microL) as determined by a spectrophotometric hemoglobin assay. Accordingly, these findings suggest that early hypothermia may fail to lessen lesion size owing to complications, such as elevated blood pressure, whereas much-delayed hypothermia is beneficial after ICH. Future experiments should assess whether counteracting the side effects of early hypothermia enhances protection.
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PMID:Delayed onset of prolonged hypothermia improves outcome after intracerebral hemorrhage in rats. 1508 12

17beta-estradiol reduces cell death after global and focal ischemia and subarachnoid hemorrhage in rodents. Presently, we tested whether estrogen improves outcome after intracerebral hemorrhage (ICH) in male rats. Rats were implanted subcutaneously with 0.05, 0.25, or 0.50 mg pellets of estrogen (21-day release) or subjected to a sham procedure. Two weeks after implantation, they were given a striatal ICH via an infusion of collagenase. The three estrogen groups had significantly smaller lesions at a 7-day survival. Some rats had core temperature measured with an implanted telemetry probe, which also measured whole-body movements. Estrogen did not affect temperature nor activity levels after ICH. A second study with 0.25 mg pellets, administered once or twice, showed persistent histologic protection (30 days) and some functional benefit (e.g., elevated beam). A spectrophotometric hemoglobin assay showed that the 0.25 mg dose significantly reduced hemorrhagic blood volume at 12 hours after ICH. Regardless, estrogen did not lessen cerebral edema at 2 days after ICH and functional benefits were not consistently found on all tests (e.g., cylinder task). In summary, estrogen pretreatment reduces injury after ICH, in part by reducing bleeding. Estrogen may thus lessen injury and improve outcome after ICH in humans.
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PMID:17beta-Estradiol pretreatment reduces bleeding and brain injury after intracerebral hemorrhagic stroke in male rats. 1567 26

The vascularization of engineered tissues in many cases does not keep up with the ingrowth of cells. Nutrient and oxygen supply are not sufficient, which ultimately leads to the death of the invading cells. The enhancement of the angiogenic capabilities of engineered tissues therefore represents a major challenge in the field of tissue engineering. The immobilization of angiogenic growth factors may be useful for enhancing angiogenesis. The most potent angiogenic growth factor specific to endothelial cells, vascular endothelial growth factor (VEGF), occurs in several splice variants. The variant with 165 amino acids both has a high angiogenic activity and a high affinity for heparin. We therefore incorporated heparin molecules into collagen matrices by covalently cross-linking them to amino functions on the collagen. Physical binding of VEGF to the heparin may then prevent a rapid clearance from the implant, while the release rate may become coupled to the degradation of the collagen matrix. The modified matrices were characterized by determination of the extent of the heparin immobilization, the in vitro degradation rate by collagenase. For testing the angiogenic properties, non-modified and heparinized collagen specimens were--either loaded with VEGF or non-loaded--subcutaneously implanted on the back of rats. Specimens were explanted after varying periods of implantation, the dry weights and the hemoglobin contents, as well as immunostained histological sections were evaluated: heparinized collagen matrices loaded with VEGF are vascularized to a substantially higher extent as compared to non-modified matrices.
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PMID:Modification of collagen matrices for enhancing angiogenesis. 1581 46


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