Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chondroitin Sulfate ABC lyase I from Proteus vulgaris is an endolytic, broad-specificity glycosaminoglycan lyase, which degrades chondroitin, chondroitin-4-sulfate, dermatan sulfate, chondroitin-6-sulfate, and hyaluronan by beta-elimination of 1,4-hexosaminidic bond to unsaturated disaccharides and tetrasaccharides. Its structure revealed three domains. The N-terminal domain has a fold similar to that of carbohydrate-binding domains of xylanases and some lectins, the middle and C-terminal domains are similar to the structures of the two-domain chondroitin lyase AC and bacterial hyaluronidases. Although the middle domain shows a very low level of sequence identity with the catalytic domains of chondroitinase AC and hyaluronidase, the residues implicated in catalysis of the latter enzymes are present in chondroitinase ABC I. The substrate-binding site in chondroitinase ABC I is in a wide-open cleft, consistent with the endolytic action pattern of this enzyme. The tryptophan residues crucial for substrate binding in chondroitinase AC and hyaluronidases are lacking in chondroitinase ABC I. The structure of chondroitinase ABC I provides a framework for probing specific functions of active-site residues for understanding the remarkably broad specificity of this enzyme and perhaps engineering a desired specificity. The electron density map showed clearly that the deposited DNA sequence for residues 495-530 of chondroitin ABC lyase I, the segment containing two putative active-site residues, contains a frame-shift error resulting in an incorrectly translated amino acid sequence.
J Mol Biol 2003 May 02
PMID:Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution. 1270 21

Proteoglycans (PGs) have been shown to play a key role in the development of many tissues. We have investigated the role of sulfated PGs in early rat lung development by treating cultured tissues with 30 mM sodium chlorate, a global inhibitor of PG sulfation. Chlorate treatment disrupted growth and branching of embryonic day 13 lung explants. Isolated lung epithelium (LgE) migrated toward and invaded lung mesenchyme (LgM), and chlorate irreversibly suppressed this response. Chlorate also inhibited migration of LgE toward beads soaked in FGF10. Chlorate severely decreased branching morphogenesis in tissue recombinants consisting of LgM plus either LgE or tracheal epithelium (TrE) and decreased expression of surfactant protein C gene (SP-C). Chlorate also reduced bone morphogenetic protein-4 expression in cultured tips and recombinants but had no effect on the expression of clara cell 10-kDa protein (CC10), sonic hedgehog (Shh), FGF10, and FGF receptor 2IIIb. Chlorate reduced the growth of LgE in mesenchyme-free culture but did not affect SP-C expression. In contrast, chlorate inhibited both rudiment growth and the induction of SP-C in mesenchyme-free cultured TrE. Treatment of lung tips and tissue recombinants with chondroitinase ABC abolished branching morphogenesis. Chondroitinase also suppressed growth of TrE in mesenchyme-free culture. Chondroitinase treatment, however, had no effect on the induction of SP-C expression in any of these cultures. These results demonstrate the overall importance of sulfated PGs to normal lung development and demonstrate a dynamic role for chondroitin sulfate PGs in embryonic lung growth and morphogenesis.
Am J Physiol Lung Cell Mol Physiol 2003 Dec
PMID:Chondroitin sulfate proteoglycans are required for lung growth and morphogenesis in vitro. 1292 82

During the initial stages of development, the notochord provides repulsive signals for dorsal root ganglion (DRG) axons via semaphorin 3A/neuropilin-1, axonin-1/SC2, and other unknown repulsive molecules. The notochord is known to produce aggrecan, one of the chondroitin sulfate proteoglycans (CSPGs). We report here that adding aggrecan to the culture medium cannot only induce DRG growth cone collapse, but also inhibit DRG axonal growth. Using cocultures composed of tissues derived from chick embryos or neuropilin-1-deficient mice treated with chondroitinase ABC, we show the direct evidence that CSPGs are involved in notochord-derived repulsion for DRG axons. At later developmental stages, CSPGs are involved in perinotochordal sheath-derived axon repulsion, but not in notochord core-derived repulsion. We further demonstrate that TAG-1/axonin-1/SC2 is not involved in mediating repulsive activities by CSPGs, but is required for notochord core-derived axon repulsion. Thus, notochord-derived multiple axon repulsions act in a spatiotemporal-specific manner to shape the initial trajectories of DRG axons.
Mol Cell Neurosci 2004 Feb
PMID:Developmental regulation of notochord-derived repulsion for dorsal root ganglion axons. 1501 39

In order to study the presence of sulphated glycoconjugates in the first mineralised layer juxtaposed to the root dentine (the hyaline layer), we have examined the early stages of molar root development by ultrastructural cytochemistry using Cuprolinic Blue combined with enzymatic pretreatment. Upper molars from 10 to 13 day-old Wistar rats were fixed in 2.5% glutaraldehyde containing 0.05% Cuprolinic Blue in 25 mM sodium acetate, pH 5.6, containing 0.3 M MgCl2. Some specimens were previously treated with heparitinase or chondroitinase ABC. Our results showed sulphated glycoconjugate--Cuprolinic Blue complexes that appeared as electron opaque ribbon-like deposits in the unmineralised hyaline layer. Few complexes were detected adjacent to the dentinal surface. These complexes were removed by heparitinase, indicating that they contained heparan sulphate chains. In contrast, the complexes found in unmineralised cementum and root dentine were removed by chondroitinase, indicating that they contained chondroitin or dermatan sulphate chains. The complexes decreased after the initiation of mineralisation of hyaline layer and root dentine and they were no longer present in stages of fully mineralisation. We conclude that the hyaline layer only contains sulphated glycoconjugates prior to mineralisation, and that they may play a role in the regulation of the mineralisation.
J Mol Histol 2004 Jan
PMID:Localisation of sulphated glycoconjugates during hyaline layer formation in rat molars by ultrastructural cytochemistry. 1532 50

The levels of arylsulfatases A and B, alpha-amylase, aspartate transcarbamylase, and gamma-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p < 0.001) increase in the activity of hepatic arylsulfatase B (ASB), aspartate transcarbamylases and gamma-glutamyl transpeptidase. A non-significant difference occurred for alpha-amylase (p < 0.3) and arylsulfatase A (p > 0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of K(m) and about a 40% increase in V(max) when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.
J Biochem Mol Biol 2004 Mar 31
PMID:Activity of some hepatic enzymes in schistosomiasis and concomitant alteration of arylsulfatase B. 1546 99

In the dorsal root entry zone (DREZ) peripheral sensory axons fail to regenerate past the peripheral nervous system/central nervous system (PNS/CNS) interface. Additionally, in the spinal cord, central fibers that regenerate into Schwann cell (SC) bridges can enter but do not exit at the distal Schwann cell/astrocyte (AC) boundary. At both interfaces where limited mixing of the two cell types occurs, one can observe an up-regulation of inhibitory chondroitin sulfate proteoglycans (CSPGs). We treated confrontation Schwann cell/astrocyte cultures with the following: (1) a deoxyribonucleic acid (DNA) enzyme against the glycosaminoglycan (GAG)-chain-initiating enzyme, xylosyltransferase-1 (XT-1), (2) a control DNA enzyme, and (3) chondroitinase ABC (Ch'ase ABC) to degrade the GAG chains. Both techniques for reducing CSPGs allowed Schwann cells to penetrate deeply into the territory of the astrocytes. After adding sensory neurons to the assay, the axons showed different growth behaviors depending upon the glial cell type that they first encountered during regeneration. Our results help to explain why regeneration fails at PNS/CNS glial boundaries.
Mol Cell Neurosci 2005 Jan
PMID:The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. 1560 38

Two species of commercially important cold water fish were investigated for content of sulfated glycosaminoglycans (GAGs) in muscle tissue by use of in vivo 35S-sulfate labeling combined with different digestions (papain, chondroitinase ABC, keratanase and nitrous acid treatment), DEAE chromatography, SDS-PAGE and histology techniques. The species investigated in this study have different gaping properties. The non-gaping species, spotted wolffish (Anarhichas minor), contained 3-4 times more 35S-sulfated anionic components than the gaping species, Atlantic cod (Gadus morhua). The higher level of sulfation in wolffish was supported by light microscopy studies using Alcian blue staining with different concentrations of MgCl2 as critical electrolyte. Furthermore, the muscular connective tissue in the non-gaping species was dominated by chondroitin sulfate (CS)/dermatan sulfate (DS), whereas the gaping species was more dominated by heparan sulfate (HS). Moreover, structural differences were observed in the junctions between the myofibers, which were more pronounced in the wolffish. The histological studies revealed that the basement membrane area was rich in acidic mucopolysaccharides in both species.
Comp Biochem Physiol B Biochem Mol Biol 2005 Mar
PMID:Sulfated glycosaminoglycans in the extracellular matrix of muscle tissue in Atlantic cod (Gadus morhua) and Spotted wolffish (Anarhichas minor). 1569 82

Secreted semaphorins are essential for neural development and continue to be expressed in subpopulations of adult neurons, where they subserve as yet unknown functions. We employed functional myc- and GFP-tagged Sema3A proteins to obtain insight in the localization of Sema3A in neuronal cells. Sema3A localized to both axons and dendrites of cortical neurons. GFP-Sema3A exhibited a characteristic punctate distribution on the surface of Neuro-2a cells, localized to migratory pathways of cultured cells, and co-localized with and induced clustering of its receptor component neuropilin-1. Treatment with excess glycosaminoglycans and chondroitinase ABC resulted in the removal of cell surface Sema3A. Heparin enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its growth cone collapsing activity. Together, these results indicate that association with proteoglycans in the extracellular matrix of neuronal cells plays an important role in the localization of the chemorepulsive guidance cue Sema3A, and that this interaction may enhance its biological activity.
Mol Cell Neurosci 2005 May
PMID:Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix. 1586 45

Adult axons in the mammalian central nervous system do not elicit spontaneous regeneration after injury, although many affected neurons have survived the neurotrauma. However, axonal regeneration does occur under certain conditions. These conditions include: (a) modification of regrowth environment, such as supply of peripheral nerve bridges and transplantation of Schwann cells or olfactory ensheathing glia to the injury site; (b) application of neurotrophic factors at the cell soma and axon tips; (c) blockade of growth-inhibitory molecules such as Nogo-A, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein; (d) prevention of chondroitin-sulfate-proteoglycans-related scar tissue formation at the injury site using chondroitinase ABC; and (e) elevation of intrinsic growth potential of injured neurons via increasing intracellular cyclic adenosine monophosphate level. A large body of evidence suggests that these conditions achieve enhanced neuronal survival and axonal regeneration through sometimes overlapping and sometimes distinct signal transduction mechanisms, depending on the targeted neuronal populations and intervention circumstances. This article reviews the available information on signal transduction pathways underlying neurotrophic-factor-mediated neuronal survival and neurite outgrowth/axonal regeneration. Better understanding of signaling transduction is important in helping us develop practical therapeutic approaches for encouraging neuronal survival and axonal regeneration after traumatic injury in clinical context.
Mol Neurobiol 2006 Apr
PMID:Actions of neurotrophic factors and their signaling pathways in neuronal survival and axonal regeneration. 1660 94

Sulfatase enzymes have important roles in metabolism of steroid hormones and of glycosaminoglycans (GAGs). The activity of five sulfatase enzymes, including steroid sulfatase (STS; arylsulfatase C), arylsulfatase A (ASA; cerebroside sulfatase), arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase), galactose-6-sulfatase (GALNS), and iduronate-2-sulfatase (IDS), was compared in six different mammary cell lines, including the malignant mammary cell lines MCF7, T47D, and HCC1937, the MCF10A cell line which is associated with fibrocystic disease, and in primary epithelial and myoepithelial cell lines established from reduction mammoplasty. The effects of estrogen hormones, including estrone, estradiol, estrone 3-sulfate, and estradiol sulfate on activity of these sulfatases were determined. The malignant cell lines MCF7 and T47D had markedly less activity of STS, ASB, ASA, and GAL6S, but not IDS. The primary myoepithelial cells had highest activity of STS and ASB, and the normal epithelial cells had highest activity of GALNS and ASA. Greater declines in sulfatase activity occurred in response to estrone and estradiol than sulfated estrogens. The study findings demonstrated marked variation in sulfatase activity and in effects of exogenous estrogens on sulfatase activity among the different mammary cell types.
J Steroid Biochem Mol Biol 2007 Jan
PMID:Steroid sulfatase, arylsulfatases A and B, galactose-6-sulfatase, and iduronate sulfatase in mammary cells and effects of sulfated and non-sulfated estrogens on sulfatase activity. 1706 91


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