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

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Query: EC:4.2.2.7 (heparinase)
1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether a recognition mechanism is involved in determination of sympathetic innervation patterns of various tissues, tissue-derived substances were applied to a restricted test surface region of dishes and the responses of cultured sympathetic neurites were examined. Sympathetic fibers exhibited a turning or ramifying response, resulting in a dense fiber growth on test regions coated with particulate (adheron) fractions of a conditioned-medium (CM) from expansor secundariorum, heart, peripheral blood vessel or abdominal aorta, whereas on test regions coated with those from lung, skeletal muscle or dorsal aorta the neurite growth was repelled and sparse fiber growth was observed. Particulate fractions of brain- or gizzard-CM had no effect. These patterns in vitro were in parallel with the dense sympathetic innervation in expansor secundariorum, heart, peripheral blood vessel and abdominal aorta, but little or no sympathetic innervation in lung, skeletal muscle and dorsal aorta in vivo. These results suggest that adheron particles may participate in determination of sympathetic innervation patterns. Activity which repels or promotes the sympathetic fiber growth was inactivated by pronase E or trypsin but not by DNase or neuraminidase. Repelling activity was lost after treatment with heparinase or heparitinase but not with chondroitinase ABC or hyaluronidase. Promoting activity was retained after treatment with these glycosidases. These results suggest that the factor(s) possessing a repellent effect is a heparan sulfate proteoglycan and one(s) possessing a promoting effect is a protein.
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PMID:Characterization of substances which promote or repel sympathetic fiber growth in vitro. 133 24

Basic fibroblast growth factor (bFGF) binds to cell surface receptors and to heparin sulfate proteoglycans. Heparan sulfate binding may limit bFGF degradation and be an obligatory step for bFGF cell interaction. Transforming growth factor-beta 1 (TGF-beta 1) is a potent regulator of proteoglycan production and composition. The possibility that TGF-beta 1 synergistically regulates bFGF activity by altering bFGF-proteoglycan interactions was investigated. TGF-beta 1 increased 125I-bFGF binding to the extracellular matrix (ECM) of Balb/c3T3 cells 2-4-fold by increasing the number of bFGF binding sites. Increased bFGF binding correlated with a 2-5-fold increase in the production of sulfated proteoglycans, including heparan sulfate proteoglycans. TGF-beta 1 selectively stimulated production of high molecular mass proteoglycans (190-300 kDa) in conditioned medium and stimulated all proteoglycans in ECM. 125I-bFGF bound to TGF-beta 1 induced proteoglycans immobilized onto cationic nylon filters. Furthermore, ECM isolated from TGF-beta 1-treated cells incorporated more mitogenically active bFGF than native ECM. The mitogenic potential of the ECM was significantly reduced by treatment with heparinase. These results suggest that the ability of TGF-beta 1 to stimulate binding of bFGF to ECM, increase ECM heparan sulfate proteoglycan, and potentiate the mitogenic activity of bFGF are linked. Thus one aspect of TGF-beta 1/bFGF synergy may involve modulation of the ECM.
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PMID:Transforming growth factor beta 1 stimulates the production of basic fibroblast growth factor binding proteoglycans in Balb/c3T3 cells. 140 Apr 36

Skin fibroblasts lines established from patients with Alzheimer's disease and old normal individuals were cultured with 35S-sodium sulfate and 3H-glucosamine. Proteoglycans were isolated and characterized. Sulfate incorporation into proteoglycans increased in Alzheimer's disease fibroblasts relative to normal controls. These increases changed the ratio of chondroitin sulfate to heparan sulfate proteoglycan from 1.4 to 1.7 (p = 0.0012) and decreased the ratio of cell to medium proteoglycans from 0.32 to 0.26 in normal and Alzheimer fibroblasts (p = 0.006), respectively. HPLC analysis of the disaccharides produced by chondroitinase ABC revealed no differences in composition between proteoglycans of Alzheimer and normal fibroblasts in either the cell or medium fraction. However, analysis of disaccharides produced by heparinase plus heparitinase showed differences in composition in the medium but not the cell fraction. delta UA-GlcNS was increased by 30% while delta UA-GlcNS-6S was reduced by 40% in Alzheimer's disease.
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PMID:Characterization of proteoglycans in Alzheimer's disease fibroblasts. 159 Jul 92

The sulfated proteoglycans in the normal human lamina cribrosa were studied by electron microscopy after cuprolinic blue dye binding. Within the cores of the laminar plates, three types of cuprolinic blue-positive proteoglycan filaments with different sizes were associated with collagen fibers. These filaments, which were partially sensitive to chondroitinase AC and chondroitinase B, were completely removed by chondroitinase ABC and were identified as chondroitin/dermatan sulfate proteoglycans. In addition, small punctate and filamentous structures that stained with cuprolinic blue were associated with the basal laminae of astrocytes and blood vessels. Enzyme chondroitinase ABC had no effect, but heparinase digested all of these basement membrane-associated structures, indicating that they represented heparan sulfate proteoglycan molecules. Keratanase did not affect any of the cuprolinic blue-positive materials. This investigation illustrates the ultrastructural distribution and morphology of proteoglycans in the human lamina cribrosa and provides baseline information for future studies regarding the roles of proteoglycan molecules in diseases such as glaucoma.
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PMID:Sulfated proteoglycans in the human lamina cribrosa. 163 36

Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have recently been shown to contain heparan sulfate proteoglycans (HSPGs). HSPGs are also present in other amyloid deposits in the brain and in systemic amyloidoses. Basic fibroblast growth factor (bFGF) is a heparin binding growth factor which is involved in angiogenesis and also has neurite promoting activity. We now report that bFGF binds avidly to extracellular NFT. Alz-50, a monoclonal antibody (MAb) to an abnormal form of tau and bFGF binding label mutually exclusive subpopulations of neurofibrillary tangles. bFGF binding is abolished by heparinase or heparitinase treatment and therefore is most likely based on the presence of HSPG. Binding of bFGF is a specific and sensitive morphological method to distinguish intra- from extracellular NFT. As intracellular NFT, which also contain HSPGs, are not labeled by bFGF binding, this finding also suggests that HSPGs are modified when the NFT become extracellular.
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PMID:Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease. 186 6

The major intracytoplasmic lesion of Alzheimer's disease is the neurofibrillary tangle (NFT), which is primarily composed of paired helical filaments (PHFs). The mechanism responsible for the formation of PHFs, as well as their insolubility and apparent heterogeneity, is unknown. We found that basic fibroblast growth factor (bFGF) binds to heparinase-sensitive sites in NFTs. bFGF binding is due to a heparan sulfate proteoglycan (HSPG) immunocytochemically identified in NFTs. In the presence of polycations (e.g., Ca2+), HSPG will bind to free carboxyl groups in NFT proteins. HSPG binding may play a role in transforming normal soluble proteins into insoluble PHFs.
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PMID:Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease. 194 Nov 2

Proliferation of smooth muscle cells is an important component of pulmonary arterial morphogenesis, both during normal development and pathologic remodeling. However, little is known of the factors that regulate smooth muscle proliferation in these vessels. To investigate the hypothesis that factors produced by endothelial cells may regulate smooth muscle cell growth, we studied the effects of culture medium conditioned by fetal bovine pulmonary arterial endothelium on proliferation of smooth muscle cells in culture. This conditioned medium contains an inhibitor of smooth muscle proliferation that is degraded by nitrous acid, heparinase, and heparitinase, but resists degradation by protease, boiling, and chondroitin ABC lyase, indicating that the inhibitor is structurally similar to heparin. Inhibitor release occurs in both growing and confluent endothelial cell cultures and in the presence and absence of serum. A growth-inhibiting proteoglycan purified to homogeneity from endothelial cell-conditioned medium has physicochemical characteristics similar to those of the prototypic basement membrane heparan sulfate proteoglycan of the Englebreth-Holm-Swarm tumor: an overall size of approximately 10(6) D, heparan sulfate chains of 60,000 D, and a buoyant density of 1.33 g/ml. Antibody raised against the tumor basement proteoglycan recognizes this endothelial heparan sulfate proteoglycan, and Western blotting after SDS-PAGE demonstrates that the core proteins of both proteoglycans migrate as a doublet at apparent molecular weights of 450,000 and 360,000 D. Heparan sulfate glycosaminoglycan prepared from purified medium proteoglycan is a potent inhibitor of smooth muscle cell growth, exhibiting activity approximately 1,000 times greater than that of heparin. These results indicate that endothelial cells cultured from fetal bovine pulmonary arteries produce a basement membrane heparan sulfate proteoglycan that is a potent inhibitor of smooth muscle proliferation. This proteoglycan may mediate endothelial regulation of smooth muscle growth during development or pathologic pulmonary arterial remodeling.
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PMID:Endothelial heparan sulfate proteoglycan. I. Inhibitory effects on smooth muscle cell proliferation. 213 6

Constituents of the bone marrow microenvironment have the capacity to influence both normal and malignant hematopoietic cell behavior. For example, HL-60 human promyelocytic leukemia cells in vitro display a more mature phenotype when grown on a bone marrow stroma-derived matrix. To elucidate which component(s) of the stromal matrix is capable of modulating HL-60 cell phenotype, matrices were treated with a variety of chemicals and enzymes prior to being used in the differentiation assay. Treatment of matrices with collagenase, pronase, chondroitinase, or chloroform:methanol:ether could not abolish the differentiation-promoting activity of bone marrow stroma. In contrast, the activity was destroyed by alkali treatment (0.5 M NaOH for 18 h) or heparinase/heparitinase enzymes. Heparin added to cultures increased maturation of HL-60 cells as determined by esterase production, Fc rosette formation, and morphological appearance. Other stromal components such as laminin, fibronectin, collagen I, collagen IV, or chondroitin sulfate did not alter the HL-60 leukemia cell phenotype. Stroma-derived matrix material which labeled with [35S]sulfate and eluted on a DEAE ion-exchange column as a high ionic fraction in 1.5 M LiCl and 7.5% sodium dodecyl sulfate contained the active fraction. A heparan sulfate proteoglycan component isolated by polyacrylamide-agarose gel electrophoresis induced a more mature HL-60 phenotype, and digestion with heparinase/heparitinase in the presence of protease inhibitors abrogated the effects on HL-60 phenotype. We conclude that a heparan sulfate-associated fraction of the bone marrow matrix plays a key role in the regulation of leukemic cell maturation.
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PMID:A heparan sulfate-containing fraction of bone marrow stroma induces maturation of HL-60 cells in vitro. 214 Feb 91

Schwann cells synthesize both hydrophobic and peripheral cell surface heparan sulfate proteoglycans (HSPGs). Previous analysis of the kinetics of radiolabeling suggested the peripheral HSPGs are derived from the membrane-anchored forms (Carey, D., and D. Evans. 1989. J. Cell Biol. 108:1891-1897). Peripheral cell surface HSPGs were purified from phytic acid extracts of cultured neonatal rat sciatic nerve Schwann cells by anion exchange, gel filtration, and laminin-affinity chromatography. Approximately 250 micrograms of HSPG protein was obtained from 2 X 10(9) cells with an estimated recovery of 23% and an overall purification of approximately 2000-fold. SDS-PAGE analysis indicated the absence of non-HSPG proteins in the purified material. Analysis of heparinase digestion products revealed the presence of at least six core protein species ranging in molecular weight from 57,000 to 185,000. The purified HSPGs were used to produce polyclonal antisera in rabbits. The antisera immunoprecipitated a subpopulation of 35SO4-labeled HSPGs that were released from Schwann cells by incubation in medium containing phosphatidylinositol-specific phospholipase C (PI-PLC); smaller amounts of immunoprecipated HSPGs were also present in phytic acid extracts. In the presence of excess unlabeled PI-PLC-released proteins, immunoprecipitation of phytic acid-solubilized HSPGs was inhibited. SDS-PAGE analysis of proteins immunoprecipitated from extracts of [35S]methionine labeled Schwann cells demonstrated that the antisera precipitated an HSPG species that was present in the pool of proteins released by PI-PLC, with smaller amounts present in phytic acid extracts. Nitrous acid degradation of the immunoprecipitated proteins produced a single 67,000-Mr core protein. When used for indirect immunofluorescence labeling, the antisera stained the external surface of cultured Schwann cells. Preincubation of the cultures in medium containing PI-PLC but not phytic acid significantly reduced the cell surface staining. The antisera stained the outer ring of Schwann cell membrane in sections of adult rat sciatic nerve but did not stain myelin or axonal membranes. This localization suggests the HSPG may play a role in binding the Schwann cell plasma membrane to the adjacent basement membrane surrounding the individual axon-Schwann cell units.
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PMID:Identification of a lipid-anchored heparan sulfate proteoglycan in Schwann cells. 217 60

The INO (inhibitor of neurite outgrowth) antibody recognizes a laminin-heparan sulfate proteoglycan complex and was isolated for its ability to functionally inhibit axonal outgrowth of peripheral neurons. Here, we examine the distribution and biochemical characteristics of INO in the early chick embryo. Because the INO antigen is sensitive to most classical fixation procedures and fixation leads to abundant nuclear staining, the antibody was directly injected into 1.5-2.5-day-old embryos prior to fixation. The distribution of the injected antibody was then observed in cryostat sections by indirect immunofluorescence. Particular attention was focussed upon regions of ongoing neural crest cell migration. The INO antigen was observed along both cranial and trunk neural crest cell migratory pathways. The antigen was seen around the basement membrane surrounding the neural tube and notochord, and underneath the ectoderm and endoderm. In addition, fibrillar staining was observed in the cranial mesenchyme and in both rostral and caudal halves of the somitic sclerotome in the trunk. The distribution pattern was identical to that previously observed for laminin or heparan sulfate proteoglycan. To confirm the nature of the INO antigen, we performed immunoprecipitations of chick embryos ranging from 1.5 to 9 days of incubation. Half of each sample was digested with heparinase prior to SDS-PAGE and silver staining. In material from young embryos, bands of 200 and 180 kD (probably corresponding to the B-chains of laminin) plus two broad smears of bands at 180-150 kD and 130-85 kD were observed without heparinase digestion. Following enzymatic digestion, the 200-kD and 180-kD bands remained, while the smears disappeared and were replaced by numerous low-molecular-weight bands. In contrast to preparations from young embryos, samples taken from embryos at day 3 or beyond did not enter the 8% gel without heparinase digestion, though the banding pattern appeared identical to younger samples after heparinase digestion in the presence or absence of Ca2+. This change in the INO antigen with age could result from an increase in the heparin-side-chains attached to similar core proteins, or from an increase in the stability of the laminin-heparan sulfate proteoglycan containing complex with time.
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PMID:Distribution and biochemical characterization of the INO antigen during chick neural crest cell migration. 225 80


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