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)

Two thrombolytic agents are mainly used in patients: streptokinase (SK) and urokinase (UK). UK from human origin is an endopeptidase which is able to convert plasminogen into plasmin. UK is only secreted by the kidney and is only found in urine which is presently the only source of extraction. Studies in man have shown that UK produces a highly reproducible state of enhanced plasma thrombolytic activity with a high fibrinolysis/fibrnogenolysis ratio and a lack of toxicity and antigenicity. The half life in Animal is short as well as the duration of fibrinolytic activity in Man. In clinical experience, positive results have been reported in pulminary embolism while the issues in myocardial infarction are controversial. Suggestive results have been registered in deep vein thrombosis, in ophthalmologic field and in desobstruction of arterio-venious shunts. No evident benefit has been noted in cerebral vascular disease. Up to now, UK has been very well tolerated.
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PMID:[Urokinase. Biochemical therapeutical and therapeutical data (author's transl)]. 6 58

Leupeptin is a small peptide microbially derived inhibitor of certain proteolytic enzymes. Using N-alpha-benzoyl-DL-arginine 4-nitroanilide as substrate, we found a novel leupeptin-sensitive proteolytic enzyme in N-methyl-N-nitrosourea(MNU)-induced rat mammary adenocarcinoma. This enzyme was apparently different from urokinase-type plasminogen activator or cathepsin B and was present in mammary tumour at levels at least 20 times higher than those in normal mammary tissue. This enzyme was separated and purified from crude extracts of MNU-induced mammary adenocarcinoma approx. 1900-fold with 34% yield. It was a trypsin-like serine endopeptidase and had a pH optimum at 7.0. The native enzyme had an apparent M(r) of 180,000 and exhibited four isoelectric points ranging from 4.3 to 5.0. Electrophoresis of denatured enzyme, however, yielded, with reduction, a major band with an apparent M(r) of 37,500 and a minor band with an apparent M(r) of 35,500. The N-terminal 23 residues of the major band were Ile1-Val2-Gly3-Gly4-Gln5-Glu6-Ala7-+ ++Ser8-Gly9-Asn10-Lys11-Xaa12-Pro13- Val14- Gln15-Val16-Xaa17-Leu18-Xaa19-Val20- Trp21-Leu22-Pro23. These and other properties of this enzyme suggested that it most closely resembles rat skin tryptase, followed by rat peritoneal mast-cell tryptase and then by tryptases from other species. The rat, like human and mouse, may carry multiple tryptase genes, and this mammary-tumour enzyme may be an additional form of rat tryptase within a new serine-proteinase family.
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PMID:Separation, purification and N-terminal sequence analysis of a novel leupeptin-sensitive serine endopeptidase present in chemically induced rat mammary tumour. 131 62

Human subcultures (third passage) of glomerular visceral epithelial cells (VEC) isolated from one month old kidney were successfully transfected by two recombinant plasmids containing the cloned oncogenes from the simian virus 40 large T antigen and H-ras gene. One postcrisis cell clone (56/10 A1) was selected, propagated and characterized. One hundred percent of the 56/10 A1 cells (current passage greater than 100th; doubling time 30 hrs) expressed the nuclear T-SV40 antigen assayed by IF; the cells failed to express H-ras (RNA blot analysis). Immortalized cells were morphologically and phenotypically compared to parental cell type (third passage). Phenotypic characterization of the 56/10 A1 cells was achieved using indirect immunofluorescence (IF) and immunogold silver staining coupled to bright field and epipolarization microscopy. Both parental and 56/10 A1 cells displayed positivity for cytokeratin, CALLA and PHM5, whereas von Willebrand factor was not detected in the two cell types. Since we have previously shown that human glomerular epithelial cells in culture synthetize plaminogen activator (PA) related compounds, we investigated the secretion pattern of these products in parental and transfected cells. Zymographic analysis of secreted PA related compounds revealed production of free urokinase (u-PA) and type 1 plasminogen activator inhibitor (PAI-1) complexed to tissular plasminogen activator (t-PA). Finally, in the transfected cells, increased cGMP generation under atrial natriuretic factor (ANF) stimulation agreed with previous work performed on nontransfected human VEC. In conclusion, the establishment of a human permanent cell line which retains most of the phenotypic features of parental glomerular visceral epithelial cells should represent a new tool to study human glomerular cell functions.
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PMID:Stable cell line of T-SV40 immortalized human glomerular visceral epithelial cells. 166 15

In the present study, methotrexate (MTX), was conjugated with a murine monoclonal antibody (79) to human common acute lymphoblastic leukemia antigen (CALLA), with human serum albumin (HSA) as an intermediary. The highest molar ratio of McAb 79:HSA:MTX in the conjugates was 1:2. 63:117. The conjugates obtained retained both antibody binding and drug activities. Although there was some loss of drug activity in binding to antibody, the toxicity of McAb79-HSA-MTX was entirely specific for the target cell, and the cytotoxicity of McAb79-HSA-MTX against CALLA+ cells was greater than that of control S13 (Anti-human urokinase)-HSA-MTX. The ratio of 79-HSA-MTX cytotoxicity to the target and non-target cells was 66:1, whereas there was no cytotoxicity to target cells when McAb79 was used only. There was no cytotoxic difference between 79-HSA-MTX and S13-HSA-MTX against CALLA- SB cells. These results suggest that the cytotoxicity of 79-HSA-MTX against CALLA leukemia cells is specific and this specificity is mediated by McAb79.
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PMID:[Preparation and cytotoxicity of McAb-HSA-MTX conjugates]. 217 64

Epidermal growth factor carrier protein (CP) is an arginine endopeptidase bound to epidermal growth factor (EGF) in vivo that processes pro-EGF to EGF and potentiates EGF action. Here, we provide a base for studying the biological functions of CP by showing that highly purified 125I-labeled CP, free of contaminating EGF, is specifically bound and internalized by normal human fibroblasts in serum-free medium. The characteristics of the binding reaction, however, were unusual and not consistent with direct interaction of CP with cell surface receptors. Subsequent experiments showed that cellular binding of 125I-labeled CP was mediated via a cell-secreted protein. We named the protein carrier protein nexin (CPN) because of its close functional similarity to protease nexin, which mediates cellular binding of thrombin or urokinase. Both CPN and protease nexin are secreted by cells, form covalent complexes with regulatory proteases in the extracellular environment, and mediate cellular binding of these proteases, apparently via a cell surface receptor for the nexin moiety of the complex. By several criteria, however, CPN and protease nexin are unique entities. This finding of a specific interaction of a growth factor carrier protein with cells suggests the possibility of additional physiological functions for these carriers in growth factor action or metabolism or both.
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PMID:Epidermal growth factor carrier protein binds to cells via a complex with released carried protein nexin. 698 Apr 18

Human pro-urokinase (pro-UK) gene was engineered for expression in mammalian cells. The stability of recombinant pro-UKs produced by two kinds of cells, Chinese hamster ovary (CHO) and human lymphoblastoid Namalwa KJM-1 cells, were compared. The pro-UK expressed in CHO cells in serum-free medium was degraded by cysteine endopeptidase secreted by CHO cells. This endopeptidase was inhibited by p-chloromercuribenzonate (PCMB) and leupeptin more efficiently than by aprotinin. On the other hand, the pro-UK expressed in Namalwa KJM-1 cells was not degraded, resulting in the stable production of pro-UK at a rate of 2-3 micrograms/10(6) cells/day by use of a gene amplification method with dihydrofolate reductase (DHFR) in serum-free medium. Thus, Namalwa KJM-1 cells showed the desired characteristics as a host cell for the production of recombinant proteins. The stability of recombinant proteins in heterologous systems may vary depending on the host cells.
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PMID:Stable production of recombinant pro-urokinase by human lymphoblastoid Namalwa KJM-1 cells: host-cell dependency of the expressed-protein stability. 776 81

The receptor for urokinase-type plasminogen activator (uPA-R) localizes uPA to the cell surface. The receptor-bound uPA converts plasminogen to the trypsin-like endopeptidase plasmin. Thus uPA is involved in the initiation of pericellular proteolysis. Pericellular proteolysis is assumed to facilitate the cellular infiltration into surrounding tissue. The uPA-R has recently been identified as a surface antigen of activated human T lymphocytes. We have characterized the uPA-R of the human CD4 T cell line Jurkat by immunological (flow cytometry), biochemical (ligand blotting), and physico-chemical (Scatchard blotting) methods. The collective data suggest that the human CD4+ T cell line Jurkat expresses a cell surface receptor for uPA similar to that of myelo/monocytes and normal T cells with regard to size, affinity, ligand specificity, and antigenicity. Binding studies using exogenous uPA and subsequent functional assays revealed that receptor-bound uPA retains its enzymatic activity. Saturation of the Jurkat cell uPA-R with exogenous uPA facilitated cellular invasion into fibrin matrices in vitro. uPA-dependent invasion was inhibited in the presence of an anti-catalytic monoclonal anti-uPA antibody. We propose that uPA-R-bound uPA may facilitate the invasiveness of uPA-R-positive T lymphocytes.
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PMID:Urokinase-type plasminogen activator enhances invasion of human T cells (Jurkat) into a fibrin matrix. 791 95

A novel single polypeptide endopeptidase of 24 kDa (24k-endopeptidase) was purified with a yield of 300-400 microg/L from conditioned medium of a bacterial strain which was identified as a new species in the genus Chryseobacterium Sp. on the basis of its 16S rDNA sequence and DNA:DNA hybridizations. The NH(2)-terminal amino acid sequence (Val-Ala-Thr-Pro-Asn-Leu-Glu-.) was not found in the availabe databases. The 24k-endopeptidase specifically hydrolyzed the Ser(441)-Val(442) peptide bond in human plasmin(ogen), with additional cleavage of the Lys(78)-Val(79) and Pro(447)-Val(448) peptide bonds, and a secondary cleavage at Lys(615)-Val(616). Thereby, plasminogen is converted into an angiostatin-like fragment containing kringles 1-4 (K1-4) and miniplasminogen (kringle 5 and the serine proteinase domain). The purified K1-4 fragment showed a comparable cytotoxicity toward endothelial cells as the elastase-derived K1-3 fragment (12.7% versus 10.6% at a concentration of 10 microg/mL). Plasminogen, bound to monocytoid THP-1 cells, was also cleaved by the 24k-endopeptidase, resulting in generation of an angiostatin-like fragment and in a decreased capacity to generate cell-associated plasmin following activation by urokinase. The 24k-endopeptidase was not efficiently neutralized by specific inhibitors against the serine, cysteine, aspartic, or matrix metalloproteinase classes of enzymes. In human plasma or serum, however, it induced only very limited plasminogen degradation, apparently due to neutralization of its activity by alpha(2)-macroglobulin. Interaction of this novel 24k-endopeptidase with plasminogen thus yields an angiostatin-like fragment and affects plasmin-mediated cellular proteolytic activity.
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PMID:Specific proteolysis of human plasminogen by a 24 kDa endopeptidase from a novel Chryseobacterium Sp. 1063 Oct 10

Extensive beta-amyloid (A beta) deposits in brain parenchyma in the form of senile plaques and in blood vessels in the form of amyloid angiopathy are pathological hallmarks of Alzheimer's disease (AD). The mechanisms underlying A beta deposition remain unclear. Major efforts have focused on A beta production, but there is little to suggest that increased production of A beta plays a role in A beta deposition, except for rare familial forms of AD. Thus, other mechanisms must be involved in the accumulation of A beta in AD. Recent data shows that impaired clearance may play an important role in A beta accumulation in the pathogenesis of AD. This review focuses on our current knowledge of A beta-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), insulin-degrading enzyme (IDE), angiotensin-converting enzyme (ACE), and the plasmin/uPA/tPA system as they relate to amyloid deposition in AD.
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PMID:beta-Amyloid degradation and Alzheimer's disease. 1704 8

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.
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PMID:Abeta-degrading enzymes in Alzheimer's disease. 1836 35


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