Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amidolytic plasmin activity of a mixture of tissue plasminogen activator (tPA) and plasminogen is enhanced by heparin at therapeutic concentrations. Heparin also increases the activity in mixtures of urokinase-type plasminogen activator (uPA) and plasminogen but has no effect on streptokinase or plasmin. Direct analyses of plasminogen activation by polyacrylamide gel electrophoresis demonstrate that heparin increases the activation of plasminogen by both tPA and uPA. Binding studies show that heparin binds to various components of the fibrinolytic system, with tight binding demonstrable with tPA, uPA, and Lys-plasminogen. The stimulation of tPA activity by fibrin, however, is diminished by heparin. The ability of heparin to promote plasmin generation is destroyed by incubation of the heparin with heparinase, whereas incubation with chondroitinase ABC or AC has no effect. Also, stimulation of plasmin formation is not observed with dextran sulfate or chondroitin sulfate A, B, or C. Analyses of heparin fractions after separation on columns of antithrombin III-Sepharose suggest that both the high-affinity and the low-affinity fractions, which have dramatically different anticoagulant activity, have similar activity toward the fibrinolytic components.
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PMID:Interaction of heparin with plasminogen activators and plasminogen: effects on the activation of plasminogen. 294 15

Chondroitin sulfate E (CSE) markedly enhanced plasminogen activation by tissue plasminogen activators (t-PAs) and urinary plasminogen activator (u-PA) in vitro; in the presence of 10 microg/ml of CSE, the potentiation factors of single chain of t-PA, two chain of t-PA and u-PA were 400, 140 and 130, respectively. Though the potentiation activity of CSE gradually decreased when it was depolymerized by chondroitinase ABC, the specific disaccharide from CSE still showed significant activity. Glycosaminoglycan (GAG) from sea cucumber, which possesses a very similar core structure to CSE, but has additional sulfated fucose branches exhibit very weak activity. These results suggested that the minimal structural requirement in CSE to enhance plasminogen activation by plasminogen activators is GlcUAbeta1-3GalNAc(4S,6S) and that additional branching sugars abolish the activity.
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PMID:Importance of GlcUAbeta1-3GalNAc(4S,6S) in chondroitin sulfate E for t-PA- and u-PA-mediated Glu-plasminogen activation. 1115 36

The serglycin proteoglycan is best known as a hematopoietic cell granule proteoglycan. It has been found that serglycin is synthesized by endothelial cells, is localized to cytoplasmic vesicles, and is constitutively secreted. Serglycin messenger RNA in human umbilical vein endothelial cells (HUVECs) and cultured human aortic endothelial cells was detected by reverse transcription-polymerase chain reaction. (35)S-sulfate-labeled secreted and intracellular proteoglycans were analyzed. It was found that 85% of the proteoglycans synthesized during culture were secreted. A core protein of the appropriate size for serglycin was detected by analysis of the chondroitinase-digested (35)S-sulfate-labeled HUVEC proteoglycans. This was the major core protein of the secreted chondroitin sulfate proteoglycans. Recombinant serglycin core protein was used to generate an antibody in chickens. A core protein identified by Western blotting of chondroitinase digests of HUVEC proteoglycans corresponded to the major (35)S-sulfate- labeled core protein. Identical results were obtained with 2 hematopoietic cell lines. Cyto-immunofluorescence showed cytoplasmic vesicular and perinuclear labeling in hematopoietic cells and HUVECs. The serglycin-containing vesicles in HUVECs are distinct from the Weibel-Palade bodies, which contain von Willebrand factor. Confocal microscopy showed that tissue plasminogen activator was distributed similarly to serglycin. Serglycin may be important for the function of these vesicles and, once secreted, for the modulation of the activity of their constituents.
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PMID:Synthesis, secretion, and subcellular localization of serglycin proteoglycan in human endothelial cells. 1115 22

The aim of using enzymes in vitreoretinal surgery is to facility PVD and create pharmacological vitrectomy. It can be achieved by liquefying the gel structure of the vitreous (synchisis) and weakening of adherence of the posterior vitreous cortex to retina (syneresis). The article reviews currently used enzymes in vitreoretinal surgery (plasmin, hyaluronidase, dispase, chondroitinase, collagenase, urokinase, TPA--tissue plasminogen activator) and presents potential profits and side-effects related to their use. Although the day when vitreous surgery is replaced by pharmacological vitreolisis remains still as a future, these enzymes hold great promise. Additionally it has been proved that enzymes can be used successfully as an intraoperative adjuvant in vitrectomy.
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PMID:[Use of enzyme in vitreoretinal surgery]. 1204 13

Paralysis resulting from spinal cord injury is devastating and persistent. One major reason for the inability of the body to heal this type of injury ensues from the local increase of glial cells leading to the formation of a glial scar, and the upregulation of chondroitin sulfate proteoglycans (CSPGs) at the site of injury through which axons are unable to regenerate. Experimental approaches to overcome this problem have accordingly focused on reducing the inhibitory properties of CSPGs, for example by using chondroitinase to remove the sugar chains and reduce the CSPGs to their core protein constituents, although this step alone does not provide dramatic benefits as a monotherapy. Using in vitro and in vivo approaches, we describe here a potentially synergistic therapeutic opportunity based on tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen (plg) into the active protease plasmin. We show that tPA and plg both bind to the CSPG protein NG2, which functions as a scaffold to accelerate the tPA-driven conversion of plg to plasmin. The binding occurs via the tPA and plg kringle domains to domain 2 of the NG2 CSPG core protein, and is enhanced in some settings after chondroitinase-mediated removal of the NG2 proteoglycan side chains. Once generated, plasmin then degrades NG2, both in an in vitro setting using recombinant protein, and in vivo models of spinal cord injury. Our finding that the tPA and plg binding is in some instances more efficient after exposure of the NG2 proteoglycan to chondroitinase treatment suggests that a combined therapeutic approach employing both chondroitinase and the tPA/plasmin proteolytic system could be of significant benefit in promoting axonal regeneration through glial scars after spinal cord injury.
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PMID:tPA-mediated generation of plasmin is catalyzed by the proteoglycan NG2. 1800 Aug 64

Various pharmacologic vitreolysis agents, including hyaluronidase, urea, plasmin, dispase, tissue plasminogen activator and chondroitinase have been tested. Pharmacologic vitreolysis can avoid the complications of surgery such as cataract, endophthalmitis, retinal hemorrhage, tear or detachment, and anesthesia related complications. Hyaluronan is a major macromolecule of vitreous. It is a long, unbranched polymer of repeating disaccharide (glucuronic acid beta (1,3)-N-acetylglucosamine) moieties linked by beta 1-4 bonds. Hyaluronan is covalently linked to a protein core, to form a proteoglycan. It plays a pivotal role in stabilizing the vitreous gel. Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, other acid mucopolysaccharides of the connective tissue. Dissolution of the hyaluronic acid and collagen complex results in decreased viscosity of the extracellular matrix. This in turn increases the diffusion rate of erythrocytes and exudates along with phagocytes through the vitreous and facilitates red blood cell lysis and phagocytosis.
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PMID:Hyaluronidase for pharmacologic vitreolysis. 1949 48