Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble and total protein content and cathepsin D activity were measured in rat mandibular bone tissue during healing of a fracture treated with proteolytic enzymes (andecalin) or protease inhibitors (contrykal) electrophoresis. Contrykal essentially elevated collagen content in mandibular bone tissue and reduced lysosomal enzymes activity. Andecalin had no noticeable effect on the levels of total protein and collagen, but it significantly increased the activity of cathepsin D. The findings evidence that local contrykal electrophoresis in the focus of injury creates an effective concentration of the drug that enhances the fracture healing and prevents the development of pyoinflammatory complications.
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PMID:[The protein content and cathepsin D activity of the mandibular bone in rats during fracture healing]. 220 91

Cathepsin D activity and type I and III collagens content in the skin of rats treated with some antiinflammatory drugs (acetylsalicylic acid, phenylbutazone, indomethacin, colchicine and prednisone) were evaluated. It was found that investigated drugs evoke increased activity of cathepsin D and decreased collagen content (mainly type I) in this tissue. The correlation between type I collagen content and proteolytic activity was noticed.
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PMID:[Increased proteolytic activity of cathepsin D in the skin of rats after administration of various anti-inflammatory drugs]. 227 Feb 95

The purified 190-kDa fibronectin fragment produced by cathepsin D can be spontaneously activated in the presence of CaCl2. This activation generates new proteolytic activities and also results in the formation of several subfragments. One of them exhibits the activity of FN-gelatinase that preferentially splits type I denatured collagen and fibronectin (see preceding paper). In this work we describe the purification and characterization of another fragment (25 kDa), issued from the same autodigest. This fragment may be activated to yield another proteinase, that splits preferentially laminin and denatured collagen type I. This enzyme will be referred as FN-laminase. Purified FN-laminase specifically reacted with antibodies against fibronectin. The specificity of bond cleavage by FN-laminase was studied with various synthetic peptides analogous to collagen repeats. FN-laminase cleaves the Ala-Gly bond in the sequence GPAGPR; the arginine residue in position P3' is important for this cleavage. The enzyme is inhibited by pepstatin A and phenylmethanesulfonyl fluoride, like retroviral aspartic proteinases. It is also inhibited by EDTA. No inhibition was obtained with 1,10-phenanthroline or 4-chloromercuribenzoate, inhibitors of Zn-metalloproteinases or cysteine proteinases, respectively.
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PMID:Potential proteolytic activity of fibronectin: fibronectin laminase and its substrate specificity. 233 18

The distribution of cathepsin D in liver with CCl4 induced cirrhosis and its involution in rats was investigated by ultrastructural cytochemistry. Besides intracellular, it was revealed the extracellular activity of cathepsin D. The reaction product was on collagen fibers near the hepatocytes and connective tissue cells as well as on the hepatocytes microvilli and on the outside part of cellular membrane of connective tissue cells (macrophage, fibroblast, Ito cells). Hence the source of extracellular cathepsin D in liver are the parenchymatous as well as nonparenchymal cell elements. The results testify that under the cirrhosis and its involution, the cathepsin D takes part in intracellular proteolysis and is secreted by hepatocytes and connective tissue cells in the intracellular space; it also takes part in extracellular catabolism of connective tissue.
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PMID:[Intracellular and extracellular activity of cathepsin D in the liver in cirrhosis and its involution]. 233 65

Malnutrition is a common finding in chronic pancreatitis and its pathogenesis is multifactorial. In 14 patients with chronic pancreatitis we assessed the dietary intake, some anthropometric indices and the concentration of some serum proteins. In muscle specimens obtained by needle biopsy we examined the DNA, RNA and non-collagen alkali-soluble protein (ASP) content. In muscle we determined also the activity of cathepsin D, an enzyme involved in intracellular myofibrillar catabolism. Protein and energy intake were lower than in the normal healthy population. Plasma protein content (an index of liver protein synthesis) was generally in the normal range, whereas anthropometry and the biochemical muscle indices were generally subnormal, suggesting a depressed muscle protein content and synthesis (evaluated, respectively, by the ASP: DNA and RNA: DNA ratios). Cathepsin D activity was lower than in controls, and the percentage of 'free' activity tended to be higher but not significantly. This study suggests that muscle protein content and synthesis are reduced in patients with chronic pancreatitis, whereas liver protein synthesis is generally preserved. Possibly as a consequence of metabolic abnormalities and/or of an inadequate protein and energy intake, the nutritional status was often abnormal in our patients and a nutritional support therapy was needed.
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PMID:Muscle biopsy studies on protein-energy malnutrition in patients with chronic relapsing pancreatitis. 242 50

Obstructive lymphedema is a pathologic condition resulting in the accumulation and stagnation of serum proteins in the lymphatics and interstitial spaces. In a canine model of obstructive lymphedema, one limb was rendered lymphedematous, and various biochemical parameters were determined in this and an unaffected control limb. Both lymph and interstitial fluid had significantly decreased acid proteinase activity (comprising mostly cathepsin D-like enzymes) and neutral proteinase activity (comprising metallo, sulfhydryl, and serine proteinases, and collagenase). Possible reasons for these decreases could be: (1) saturation of macrophages and their surrounding environment with whole or partially digested proteins, or (2) elevation in the levels of circulating inhibitors like alpha 2-macroglobulin. The lymphedematous skin was significantly thicker than control skin and had elevated levels of collagen. However, unlike some fibrotic conditions, the relative proportions of types I, III, and V collagen, as determined by pepsin solubilization and neutral salt fractionation of the collagen fibrils, were similar to those found in normal skin. It is speculated that a decrease in the breakdown of collagen by collagenase and a continuing synthesis of collagen by fibroblasts led to an imbalance in favor of collagen deposition in the skin.
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PMID:Protein metabolism and fibrosis in experimental canine obstructive lymphedema. 244 62

The dynamics of the biological response of pulmonary tissue to silica dust (silica earth from Piotrowice, Poland, recommended as a domestic reference fibrogenic standard) was studied in rats after single-shot intratracheal instillation of a suspension of 20 mg of the dust for one, three, and seven months. Silica dust provoked pronounced pulmonary fibrosis as inferred from increased collagen content together with pathomorphological alteration (silicotic nodules). The lung burden of silica dust affected the lysosomal subfraction as manifested by an increase in its protein content with concomitant stimulation (release and presumably induction) of beta-glucuronidase and cathepsin D and a transient (up to three months) stimulation of lipid peroxidation. Stimulation of activity of lysosomal enzymes and lipid peroxidation mediated by silica dust may reflect destructive metabolic processes resulting in the development of pulmonary fibrosis as the sign of a pathological repair mechanism. The extent of the effects brought about by silica earth testify that it may be recommended as a reference standard for evaluating the potential health hazard from industrial exposure to dusts containing SiO2.
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PMID:Silica earth provoked lung fibrosis with stimulation of lysosomal enzymes and lipid peroxidation in rats. 283 69

In an attempt to clarify the roles of proteases in the developmental mechanisms of hypertensive vascular lesions, changes in activities of aortic elastase, collagenase, and cathepsin D in spontaneously hypertensive rats (SHR) and renal hypertensive rats were biochemically investigated. In SHR, elastase activity initially showed a significant increase, once two-fold higher than that in the control; but the activity tended to decrease earlier than that in the control. In both SHR and normotensive control rats collagenase activities tended to increase with advancing age. The activity in SHR was two-fold higher than that in the control at all ages examined. In both younger SHR and normotensive rats cathepsin D activities proved to be increased with advancing age, while in old rats the activities tended to decrease. The activity in SHR was three- to fivefold higher than that in the control at all ages examined. In renal hypertensive rats, the activities of elastase, collagenase, and cathepsin D increased gradually with increasing blood pressure, at levels significantly higher than those in the control. These findings suggest that the metabolisms of proteins such as elastin and collagen, expressed by these enzyme activities, are accelerated under hypertensive conditions.
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PMID:Elastase, collagenase, and cathepsin D activities in the aortas of spontaneously hypertensive and renal hypertensive rats. 300 14

The interaction of UICC crocidolite asbestos with biological membranes in vivo was studied in rats after a single intratracheal dose of a suspension of 20 mg of fibres per rat. Development of lung fibrosis (increased level of hydroxyproline, a collagen index together with corresponding pathomorphological alteration) confirmed the penetration of crocidolite fibres into the lungs in the course of seven months exposure. The pulmonary deposition of crocidolite affected the lysosomal membranes of lung cells as manifested by (1) enhanced lipid peroxidation with (2) stimulation (release) of activity of beta-glucuronidase and cathepsin D. Enhanced lipid peroxidation and activity of beta-glucuronidase may contribute to the delayed, carcinogenic effects of crocidolite asbestos.
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PMID:Enhanced lipid peroxidation and lysosomal enzyme activity in the lungs of rats with prolonged pulmonary deposition of crocidolite asbestos. 303 Mar 91

To study the changes in collagen metabolism that occur in the pathogenesis of pulmonary fibrosis, female rats were exposed to 0, 0.57, and 1.1 ppm ozone for 19 hr/day for 11 days and sacrificed 12 or 60 days after initiation of exposure. The lungs of rats sacrificed at 12 days after initiation of exposure to 1.1 ppm had interstitial pneumonia characterized by a mixed inflammatory cell infiltrate, type II cell hyperplasia, and fibroplasia, a proliferation of the collagen-producing cells; increased cathepsin D and macrophage elastase activity, indicating macrophage-induced proteinolysis; a reduced percentage of the increased collagen production that was ultrafilterable, indicating a decreased rate of intracellular degradation of newly produced collagen prior to its secretion; and increased lavage fluid hydroxyproline, indicating turnover of extracellular collagenous matrix. Reduced intracellular collagen degradation correlated directly with both increased net collagen production and fibroplasia in rats exposed to 1.1 ppm ozone for 11 days. These changes preceded an increased total lung collagen and the development of modest fibroplasia and fibrosis in the alveolar duct regions by 60 days after the 1.1 ppm ozone exposure was initiated.
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PMID:Changes in collagen metabolism and proteinolysis after repeated inhalation exposure to ozone. 303 Jul 98


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