Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aspartic endopeptidase cathepsin D was demonstrated in post mortem human brain by means of the peroxidase-antiperoxidase technique. The enzyme protein was found to be present in multiple neurons as well as in some glial cells. In embryonic nervous tissue cathepsin D was detected as early as at the 12th gestational week. During neuroontogenesis there was a continuous increase in cathepsin D immunoreactivity.
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PMID:Immunohistochemical analysis of the distribution of cathepsin D throughout human nervous system with reference to developmental aspects. 357 73

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.
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PMID:Histologic assessment of cathepsin D in osteoarthritic cartilage. 376 40

Cathepsin D is an acidic endopeptidase that has been found in the cytoplasm of neurons and other cells. To test the hypothesis that the cellular content or distribution of cathepsin D may serve as a marker of neuronal differentiation in childhood neoplasia, we performed an immunocytochemical study of the cathepsin D content of tumors that occurred in 49 pediatric patients. We found diffuse, moderate to heavy staining primarily in differentiating neurogenous tumors and minimal staining in one Wilms' tumor, one Ewing's sarcoma, and one rhabdomyosarcoma. Benign reactive histiocytes stained intensely in most tumors. We concluded that although the presence of cathepsin D in malignant cells is not diagnostic of neural tumors, it may serve as a marker for cellular maturation in neuroblastomas and as a marker of macrophage infiltration in human tumors.
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PMID:Cellular distribution of cathepsin D in childhood tumors. 383 55

The action of three previously isolated electrophoretically homogeneous brain proteinases--cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5), and high-molecular-weight aspartic proteinase (Mr = 90K; EC 3.4.23.-)--on human angiotensins I and II has been investigated. The products of enzymatic hydrolysis have been identified by thin-layer chromatography on Silufol plates using authentic standards and by N-terminal amino acid residue analysis using a dansyl chloride method. Cathepsin D and high-molecular-weight aspartic proteinase did not split angiotensin I or angiotensin II. Cathepsin B hydrolyzed angiotensin I via a dipeptidyl carboxypeptidase mechanism removing His-Leu to form angiotensin II, and it degraded angiotensin II as an endopeptidase at the Val3-Tyr4 bond. Cathepsin B did not split off His-Leu from Z-Phe-His-Leu. Brain cathepsin B may have a role in the generation and degradation of angiotensin II in physiological conditions.
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PMID:Action of brain cathepsin B, cathepsin D, and high-molecular-weight aspartic proteinase on angiotensins I and II. 391 Oct 93

This study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4 mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedimentable acid phosphatase was seen in either organ. The effects we observed are much more marked for cardiac cathepsin D; this is in good agreement with the cardiac specificity of DXR-induced cardiotoxicity with long-term administration and suggests that lysosomes could play a role in the pathogenesis of this phenomenon.
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PMID:Lysosomal alterations in heart and liver of mice treated with doxorubicin. 400 46

Rabbit synovial fibroblasts in monolayer culture secrete a specific collagenase and a neutral endopeptidase into their serum-free culture medium. The rate of secretion of these two enzymes is increased after the ingestion and storage of latex particles within the vacuolar system of the cells. The increased rates of secretion of the neutral enzymes are stable for over 2 wk in the absence of a further phagocytic bout. In constrast there is little change in the extracellular levels of two lysosomal hydrolases, cathepsin D and beta-glucuronidase. The increase in the secretory rates for the two neutral enzymes is related to the number of latex particles ingested by the cells, and increases of up to 12-fold over the nonphagocytosing cultures were observed. A variety of other materials including mycostatin particles and dextran sulfate also induced increases in the secretion of collagenase. These results are discussed in relation to the turnover of connective tissue matrix macromolecules.
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PMID:Stimulation by endocytosis of the secretion of collagenase and neutral proteinase from rabbit synovial fibroblasts. 437 92

The content and distribution of cathepsin D, a lysosomal acidic endopeptidase, were determined by immunochemical methods in rat sciatic nerve near the site of a ligature or after exposure of animals to neurotoxins. In normal sciatic nerve, cathepsin D was localized predominantly in the perinuclear regions of Schwann cells. In ligated nerve, cathepsin D increased equally in both the proximal and distal nerve segments adjacent to the ligature. Although orthograde and retrograde axonal transport of cathepsin D may have contributed to this increase, immunocytochemical methods indicated that Schwann cells or other phagocytic cells accounted for the bulk of the increased cathepsin D content of nerve. Axonal function was nontraumatically altered by the administration of 2,5-hexanedione, acrylamide, B,B'-iminodipropionitrile or zinc pyridinethione. Exposure to any of these neurotoxins raised cathepsin D content throughout the sciatic nerve twofold or more, and greater amounts of immunoreactive cathepsin D in the cytoplasm of Schwann cells could be demonstrated immunocytochemically. These results indicate that changes in cathepsin D content of Schwann cells may be a reflection of their catabolic activity. The increased Schwann cell cathepsin D content in toxic axonopathies is further proof for an enhanced Schwann cell role as a phagocyte resulting from axonal injury.
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PMID:Changes in sciatic nerve cathepsin D after ligation or exposure to neurotoxins. 618 44

gamma-Endorphin is a naturally occurring biologically active peptide that is produced by an endopeptidase activity cleaving its precursor beta-endorphin. This enzyme was termed gamma-endorphin generating enzyme (gamma-EGE). In order to quantitate gamma-EGE activity by means of a simple and sensitive assay two synthetic peptides derived from the sequence surrounding the gamma-EGE cleavage site in beta-endorphin were tested as substrates. One of these peptides Ac-Val-Thr-Leu-Phe-Lys-NHCH3 fulfilled all criteria for a suitable gamma-EGE substrate. The peptide was exclusively cleaved at the correct bond for gamma-EGE upon incubation with brain synaptic membranes, and this cleavage was inhibited by the naturally occurring substrate beta-endorphin. The peptide was insensitive to cleavage by exopeptidases and cathepsin D. Addition of a 14C-labeled methyl group at the lysine residue of this peptide by reductive methylation did not alter its properties as a substrate for gamma-EGE activity. The use of the 14C-labeled peptide allowed sensitive quantitation of its radioactive products after simple separation by hydrophobic chromatography on minicolumns containing polystyrene beads. gamma-EGE activity increased linearly with a protein concentration and incubation time. This assay can be used for reliable quantitation of gamma-EGE activity and permits investigations on the regulation of gamma-endorphin production.
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PMID:Quantitation of the endopeptidase activity generating gamma-endorphin from beta-endorphin in rat brain synaptic membranes by a radiometric assay. 620 8

The distribution of cathepsin D, an acidic endopeptidase, was localized by immunocytochemistry in human skeletal muscle obtained from 34 persons with a variety of neuromuscular disorders. Normal human skeletal muscle contained small amounts of cathepsin D, all of which was found close to the sarcolemmal membrane. Immunoreactive cathepsin D was present in the cytoplasm of many infiltrating phagocytic cells and was increased in skeletal muscle fibers from patients with muscular dystrophies, inflammatory myopathies, rhabdomyolysis, acid maltase deficiency, and neurogenic atrophy. In cases of Duchenne type muscular dystrophy, the increase in cathepsin D was especially prominent in small regenerating fibers, in which it was visualized at the ultrastructural level in lysosome-like organelles and extralysosomal locations. The function of cathepsin D in skeletal muscle is unclear, but the present findings suggest a possible role in muscle regeneration and repair. Such a role would necessitate careful selection of drugs which interfere with proteolytic activity if they are to be used as therapeutic agents in treating neuromuscular diseases.
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PMID:Immunocytochemical studies of cathepsin D in human skeletal muscle. 633 8

Rabbit thyroids contain cathepsin D (CD) and several thiol endopeptidases including cathepsin B and three newly described enzymes (cathepsins 180K, 110K, and 45K). The present paper assesses the relative physiological importance of these enzymes in thyroglobulin degradation in rabbits. Thyroidal thiol endopeptidase [thiol thyroglobulin hydrolase (thiol TgH)] activity increased in the absence of changes in CD activity in animals treated with 10 U bovine TSH. Peak enzyme activity occurred 24 h after injection of hormone. After 20 U bovine TSH, thiol endopeptidase activity increased by approximately 100%, whereas CD increased by 50%. The increase in thiol enzyme activity was attributed both to cathepsin B and to the other thiol endopeptidases. The lysosomal acid hydrolases acid phosphatase and dipeptidyl peptidase II were unaffected by TSH at either dose level. Thiol TgH activity, but not CD activity, was decreased in thyroids of rabbits treated with T4 [5 micrograms/(100 g BW X day)] for 1 week. All thyroidal acid hydrolases examined were suppressed in animals receiving T4 for 3 weeks. Thiol TgH activity was localized primarily to a lysosome-enriched fraction of thyroid homogenates. Our results suggest that the thiol proteases probably are the most important endopeptidases in thyroglobulin hydrolysis in vivo and that their activities are influenced by TSH.
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PMID:Stimulation of thyroidal thiol endopeptidases by thyrotropin. 636 Jun 67


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