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

---

Query: EC:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lysosomal endopeptidase cathepsin D is the most abundant proteinase in chondrocytes. Its significance in the pathogenesis of cartilage matrix proteoglycan (PG) degradation in osteoarthritis (OA) is unclear. The extracellular localization of cathepsin D and its potential spatial relationship to areas of PG depletion has been studied in human femoral head OA cartilage. Enzyme was identified by indirect immunofluorescence using rabbit antisera developed against a highly purified cathepsin D preparation. PG distribution was assessed in parallel sections by safranin O staining. Specimens were selected to include regions of cartilage having minimal structural and cellular alterations, severe reduction in thickness, hypocellularity, multicellular chondrocyte clusters and varying degrees of PG loss. Cathepsin D was identified in chondrocytes. When overlying fibrous connective tissue pannus was present, extracellular enzyme was predominantly localized to the cartilage-pannus interface. Cathepsin D could not be demonstrated extracellularly in areas of cartilage that were partially or totally devoid of PG. Chondrocytes in damaged regions, particularly in the superficial and upper transitional zones showing diffuse hypercellularity and/or "brood" clusters, contained increased enzyme staining. Results fail to support a role for cathepsin D in extracellular matrix PG degradation. The potential significance of this enzyme in the pathogenesis of OA would appear relegated to intracellular catabolism. Its intracellular increase at pathologic sites is consistent with enhanced catabolic activity in such regions.
...
PMID:Histologic assessment of cathepsin D in osteoarthritic cartilage. 376 40

Proteoglycans from bovine nasal septa and from the Swarm rat chondrosarcoma were isolated as aggregates (PGC) and as monomers (PGS). Portions of the PGC preparations were degraded with cathepsin D or chondroitinase AC. Chondroitin sulfates were isolated by differential precipitation from alkaline digests of the PGS from bovine nasal septa. The effects of these preparations at concentrations up to 2 mg/ml on the precipitation of tricalcium phosphate in vitro at pH 7.8 in 16 hours at 25 degrees C were ascertained. To this end, the amounts of calcium and phosphate in the precipitates and in the supernates were determined. The PGC preparations were found to be very effective inhibitors; in the presence of 2 mg/ml, precipitate did not form. The PGS preparations were less effective than the PGC preparations; in the presence of 2 mg/ml, about 20% as much calcium phosphate precipitated as in their absence. The chondroitinase AC-degraded preparations at concentrations equivalent to 2 mg/ml of the PGC preparations were approximately as effective as the PGS preparations. On the other hand, the cathepsin D-degraded PGC preparations and the chondroitin sulfate chains were relatively poor inhibitors. Although the viscosity of the solutions may have influenced the rate at which the precipitates settled to the bottom of the tubes, the amounts of the tricalcium phosphate formed were related to the composition and concentration of the proteoglycan preparations.
...
PMID:Role of proteoglycans in endochondral ossification: inhibition of calcification. 393 96

In recent years the lysosomal cathepsins have been implicated as important agents in the physiological degradation of various cartilages. In the present study, the nature of cathepsin present in human articular cartilage was investigated by microtechniques and a possible role for cathepsins in the cartilage degradation observed in osteoarthritis was sought. The results of this study indicated that the hemoglobin and proteoglycan-digesting activity in the human cartilage observed is predominantly that of a cathepsin D-type enzyme. This cathepsin D-type enzyme activity was present in two to three times greater amounts in yellowish or ulcerated articular cartilage from patients with primary osteoarthritis than in control "normal" human cartilages. The human cathepsin D-type enzyme, as well as a highly purified cathepsin D from bovine uterus degraded proteoglycan subunit (PGS) maximally at pH 5. Both enzyme preparations were inactive on hemoglobin at pH 6-8, but degraded PGS considerably at neutral pH. The activity of the human cathepsin extract was not affected by reagents which inhibit or activate cathepsins A and B. Neutral proteases which are active on hemoglobin or are inhibited by diisopropylfluorophosphate (DFP) were not detected in these preparations, but contamination by another type of neutral protease cannot be excluded. Chloroquine inhibited the degradation of PGS at neutral pH by the human cartilage enzyme extract.
...
PMID:The action of cathepsin D in human articular cartilage on proteoglycans. 426 83

Specific anti-(rabbit cathepsin D) serum, previously shown to inhibit cathepsin D, arrested the intracellular digestion of sheep IgG and radiochemically labeled hemoglobin and proteoglycan in rabbit alveolar macrophages. In the presence of antiserum, cells remained viable, but became very vacuolated. Both sheep IgG and hemoglobin were demonstrated immunocytochemically in vacuoles most of which could also be shown to contain cathepsin D. When the antiserum was removed, cells regained their normal morphology, and digestion of endocytosed proteins returned to normal. These results indicate that cathepsin D can be inhibited within lysosomes of viable cells, in which it plays a major role in the intracellular digestion of certain proteins.
...
PMID:Immunoinhibition of intracellular protein digestion in macrophages. 426 7

Proteolytic enzymes have been studied in extracts of human articular cartilage by the use of micromethods. The digestion of hemoglobin at pH 3.2 and of cartilage proteoglycan at pH 5 was shown to be due chiefly to cathepsin D. Cathepsin D was purified 900-fold from human patellar cartilage. Its identity was established by its specific cleavage of the B chain of insulin. At least six multiple forms of cathepsin D are present in cartilage; these corresponded to bovine forms 4-9. Cathepsin D had no action on proteins at pH 7.4. However, cartilage extracts digested proteoglycan, casein, and histone at this pH. The proteolytic activities against these three substrates were purified about 170-, 160-, and 70-fold, respectively. Each activity appeared in multiple forms on DEAE-Sephadex chromatography. The three activities appear to be different since cysteine inhibited casein digestion, aurothiomalate inhibited histone digestion, and neither inhibited proteoglycan digestion. Tests with a wide range of inhibitors and activators suggest that these three activities differ from other neutral proteases described in the literature.
...
PMID:Neutral proteases and cathepsin D in human articular cartilage. 427 25

Extracts of rheumatoid synovial tissue obtained at surgical synovectomy contained neutral proteinases as well as cathepsin D. The neutral proteinase activity was particle-bound but could be solubilized by 1 M MgCl2. About half of the solubilized activity adsorbed to aproptinin-Sepharose at pH 7.5 and was desorbed at pH 3.3. This activity was shown to be due to leukocyte elastase and cathepsin G by enzymological and immunological criteria. The neutral proteinase activity that did not adsorb to aprotinin-Sepharose was not due to elastase or cathepsin G. It was able to hydrolyse proteoglycan and was inhibited by diisopropylfluorophosphate, soybean and lima bean trypsin inhibitors. It was, therefore, a serine proteinase. Its inhibition characteristics were different from those of plasmin, kallikrein or thrombin. All of the neutral proteinase activity of synovial extracts was attributable to serine proteinases, no evidence of metallo-proteinases was found. The possible role of the neutral proteinases in the degradation of the matrix of cartilage is discussed. A simple procedure for purifying leukocyte elastase and cathepsin G is described as well as the raising of specific antisera to these enzymes.
...
PMID:Identification of proteinases in rheumatoid synovium. Detection of leukocyte elastase cathepsin G and another serine proteinase. 615 6

Proteinases are thought to be responsible for cartilage and bone erosion noted in chronic inflammatory conditions. Suramin [8-(3-benzamindo-4-meta-1-benzamindo)naphthalene-1,3,5-trisulfonic acid], 10(-5) and 10(-4) M, inhibited the release of a mouse macrophage-derived cartilage proteoglycan-degrading enzyme. At 10(-5) M it antagonized the activity of beta-glucuronidase and cathepsin D derived from the mouse macrophage, as well as similar enzymes secreted by rat macrophages in vivo. When cultured at 10(-4) M with rabbit knee cartilage, it antagonized the autolytic release of proteoglycan, indicating an inhibitory activity against a chondrocyte-derived neutral proteinase. After in vivo treatment at 10 mg/kg/day s.c., it was ineffective in preventing the cartilage and bone erosion noted in the adjuvant arthritic rat.
...
PMID:Divergent effects of suramin on in vitro and in vivo assays of cartilage degradation. 634 39

Cultured tissue slices from normal immature rabbit articular cartilage released latent neutral metalloproteinases into serum-free medium. On activation with 4-aminophenylmercuric acetate, these metalloproteinases could degrade collagen, proteoglycan, and gelatin. Also produced were an acid proteinase with the properties of cathepsin D and an inhibitor of the neutral metalloproteinases. The appearance of both the proteinases and the inhibitor in the culture medium could be prevented by incubation of cultures with cycloheximide. The active and latent forms of the proteinases were characterized using Ultrogel AcA 54 chromatography.
...
PMID:Characterization of latent and active forms of cartilage proteinases produced by normal immature rabbit articular cartilage in tissue culture. 634 45

Cathepsin D, the major lysosomal aspartic proteinase, is responsible for the autolysis of cartilage at slightly acidic pH, and it has been suspected of making a significant contribution to the breakdown of the living tissue, such as in stimulated by retinol. Our finding, however, has been that neither inhibitory antibodies against cathepsin D, nor chemical inhibition with pepstatin, significantly decreases the rate of degradation of proteoglycan in the organ culture system. Most of the other proteinase inhibitors tested were similarly ineffective, although the EDTA and 1,10-phenanthroline inhibited the resorption by a cytotoxic effect. We conclude that although cartilage matrix degradation has clear characteristics of proteolytic process, the identity of the enzyme(s) responsible remains obscure.
...
PMID:Evidence that extracellular cathepsin D is not responsible for the resorption of cartilage matrix in culture. 679 7

1. Proteolytic enzymes are likely to play the main role on the proteoglycan (PG)-degrading activity of rheumatoid synovium. In this paper, the presence of cathepsin D, cathepsin B, lysosomal elastase and cathepsin G in rheumatoid synovium is established by isolation, purification, and characterization of these proteases. 2. The degradation of MgCl2-extracted PG from bovine nasal cartilage was performed by using these proteases and the property of the products was studied by the viscosity, Sepharose CL-4B chromatography, Agarose/polyacrylamide-gel electrophoresis, hexosamine analysis and amino acids analysis. 3. These proteases reduced the viscosity of PG solutions and the reaction was inhibited by addition of pepstatin, antipain, elastatinal and chymostatin for each protease. 4. The size and chemical composition of the degradation products varied with the different proteases. Of the four proteases, cathepsin G produced the largest glycosaminoglycan multi-chain peptides and cathepsin B produced the smallest contained chondroitin single-chain peptide. Each protease specifically split PG core protein and the degradation products particularly indicated the characteristic structure of core peptides. 5. The results suggest that these proteases may be contributed to the breakdown of cartilage PG in rheumatoid arthritis.
...
PMID:[Studies on degradation of cartilage proteoglycan by rheumatoid synovial tissue. Part II: On the property of acid and neutral proteases obtained from rheumatoid synovial tissue (author's transl)]. 703 96


<< Previous 1 2 3 Next >>

---