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:3.1.6.4 (chondroitinase)
2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morquio syndrome (mucopolysaccharidosis IV) presents with multiple bone dysplasia and is characterized by the inability to degrade keratan sulfate due to deficient N-acetylgalactosamine-6-sulfate sulfatase in Morquio A syndrome and deficient beta-D-galactosidase in Morquio B syndrome. The aim of our study was to investigate into the pathogenetic mechanism as it is not clear whether the accumulation of keratan sulfate is toxic for osteoblasts or inhibits osteoblast activity as e.g. bone resorption. The glycosaminoglycans keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-4,6-sulfate and hyaluronic acid were tested in rat neonatal calvarian cultures for their effects on bone resorption, osteoblast activity and toxicity. Bone resorption was evaluated by calcium release into the medium, osteoblast activity by the determination of alkaline phosphatase and toxicity by measuring lactate dehydrogenase in the culture media. Keratan sulfate had no effect on bone resorption but inhibited osteoblast activity at the low, nontoxic concentration of 10 ng per ml organ culture supernatant significantly (p<0.05). At a concentration of 100 ng per ml keratan sulfate revealed toxic effects as reflected by significantly (p<0.05) elevated lactate dehydrogenase activity. None of the other glycosaminoglycans inhibited osteoblast activities. Heparan sulfate showed at toxic levels (10 microg per ml supernatant) significantly increased bone resorption (p<0.05) accompanied by increased alkaline phosphatase activity. The specific keratan sulfate effects of inhibiting osteoblast activity and toxicity towards bone, which were never tested before, suggest a role for this glycosaminoglycan in the pathogenesis of bone dysplasia in Morquio syndrome.
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PMID:The effects of acid glycosaminoglycans on neonatal calvarian cultures--a role of keratan sulfate in Morquio syndrome? 927 6

Bovine chromogranin A (CgA), together with secreted alkaline phosphatase (SEAP) as an external control for apical secretion were expressed in MDCK cells to test if CgA contains sorting signals for polarized secretion. CgA, SEAP, and the endogenous apical marker GP80 were secreted 75-80% apically. Basolateral secretion of SEAP was inhibited 40% by ammonium chloride. Sulfate labeling and digestion with chondroitinase ABC revealed a 120 kDa proteoglycan-CgA and 75 kDa CgA. Inhibition of proteoglycan synthesis did not affect apical secretion of CgA. As CgA is not N-glycosylated, we used tunicamycin to test if cellular N-glycosylation is required for apical sorting. Tunicamycin reversed the polarity of secretion of CgA to the basolateral side. These results suggest that CgA contains dominant apical and recessive basolateral sorting information.
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PMID:Polarized secretion of the regulated secretory protein chromogranin A. 1075 75

The results reported here show that sodium fluoride (NaF) at low concentration (up to 10 microM) increased four times the proliferation rate of avian osteoblasts in culture. Also NaF increases, in a concentration dependent manner, 10 times the alkaline phosphatase activity. However, NaF decreased the incorporation of 35S-sulfate into proteoglycans (PGs) synthesized by osteoblasts (60-65%). Also, we observed that PGs synthesized in the presence of NaF (50 microM) exhibited a higher sensitivity to chondroitinase ABC than PGs synthesized by osteoblasts in the absence of NaF, suggesting an increase in the chondroitin sulfate moieties associated with the core protein of PGs. The modification of glycosaminoglycan (GAG) chains composition was evidenced also by change in the mean charge density of the PGs observed by ion exchange chromatography. Since the ratio of 35SO4/3H-glucosamine incorporated into PGs was similar in the presence and in the absence of NaF (8.2 and 7, respectively), it is not possible to explain differences in mean charge density by changes in the sulfation extent of PGs. No differences were observed in the hydrodynamic size of PG synthesized in the presence of NaF, nor in the hydrodynamic size of the GAG chains. According to these results, we speculate that the stimulatory effect of fluoride on bone mineralization may be mediated, in part, by the changes in the rate of synthesis or in the structural characteristics of bone PGs. The changes produced by fluoride in PGs suggest that these molecules play an inhibitory role in the bone mineralization process.
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PMID:Sodium fluoride induces changes on proteoglycans synthesized by avian osteoblasts in culture. 1174 4

Apocrine and eccrine sweat glands are distinct in function, although they are closely related to each other developmentally and morphologically. In certain sweat gland tumors, it is difficult to differentiate between eccrine or apocrine sweat glands. Therefore, this paper reviews histochemical and immunohistochemical markers to differentiate apocrine and eccrine sweat glands with the aim of better understanding the structural and functional characteristics of these sweat glands. Specific markers for apocrine sweat glands are as follows: neuraminidase sensitive anionic sites detected by cationic colloidal gold at pH 2.0, and mitochondrion-like secretory granules that have epidermal growth factor-like antigenicity. The following antibodies react with apocrine sweat glands but not with eccrine sweat glands; the antibodies raised against 70 kDa glycoprotein purified from human milk fat globule membranes, and HMFG-1 (1.10.F3) monoclonal antibody produced by immunizing mice with defatted human milk fat globule membranes. Markers for eccrine sweat glands are as follows: dark cell granules that have chondroitinase ABC sensitive anionic sites detected by cationic gold at pH 2.0 after pretreatment with EGTA, and intercellular canaliculi with high activity of alkaline phosphatase. CEA and GCDFP-15 are expressed in both eccrine and apocrine sweat glands. Anti-EMA monoclonal antibody (E29) stains both eccrine and apocrine sweat glands.
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PMID:Histochemical and immunohistochemical markers for human eccrine and apocrine sweat glands: an aid for histopathologic differentiation of sweat gland tumors. 1176 85

An immunoglobulin superfamily neuronal adhesion molecule, Contactin, has been implicated in axon guidance of spinal sensory neurons in Xenopus embryos. To identify the guidance signaling molecules that Contactin recognizes in tailbud embryos, an in situ binding assay was performed using recombinant Contactin-alkaline phosphatase fusion protein (Contactin-AP) as a probe. In the assay of whole-mount or sectioned embryos, Contactin-AP specifically bound to the notochord and its proximal regions. This binding was completely blocked by either digestion of embryo sections with chondroitinase ABC or pretreatment of Contactin-AP with chondroitin sulfate A. When the spinal cord and the notochord explants were co-cultured in collagen gel, growing Contactin-positive spinal axons were repelled by notochord-derived repulsive activity. This repulsive activity was abolished by the addition of either a monoclonal anti-Contactin antibody, chondroitin sulfate A or chondroitinase ABC to the culture medium. An antibody that recognizes chondroitin sulfate A and C labeled immunohistochemically the notochord in embryo sections and the collagen gel matrix around the cultured notochord explant. Addition of chondroitinase ABC into the culture eliminated the immunoreactivity in the gel matrix. These results suggest that the notochord-derived chondroitin sulfate proteoglycan acts as a repulsive signaling molecule that is recognized by Contactin on spinal sensory axons.
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PMID:Repulsive guidance of axons of spinal sensory neurons in Xenopus laevis embryos: roles of Contactin and notochord-derived chondroitin sulfate proteoglycans. 1617 71

Cell surface heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans have been implicated in a multitude of biological processes, including embryonic implantation, tissue morphogenesis, wound repair, and neovascularization through their ability to regulate growth factor activity and morphogenic gradients. However, the direct role of the glycosaminoglycan (GAG) sugar-side chains in the control of human mesenchymal stem cell (hMSC) differentiation into the osteoblast lineage is poorly understood. Here, we show that the abundant cell surface GAGs, HS and CS, are secreted in proteoglycan complexes that directly regulate the bone morphogenetic protein (BMP)-mediated differentiation of hMSCs into osteoblasts. Enzymatic depletion of the HS and CS chains by heparinase and chondroitinase treatment decreased HS and CS expression but did not alter the expression of the HS core proteins perlecan and syndecan. When digested separately, depletion of HS and CS chains did not effect hMSC proliferation but rather increased BMP bioactivity through SMAD1/5/8 intracellular signaling at the same time as increasing canonical Wnt signaling through LEF1 activation. Long-term culturing of cells in HS- and CS-degrading enzymes also increased bone nodule formation, calcium accumulation, and the expression of such osteoblast markers as alkaline phosphatase, RUNX2, and osteocalcin. Thus, the enzymatic disruption of HS and CS chains on cell surface proteoglycans alters BMP and Wnt activity so as to enhance the lineage commitment and osteogenic differentiation of hMSCs.
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PMID:Disruption of heparan and chondroitin sulfate signaling enhances mesenchymal stem cell-derived osteogenic differentiation via bone morphogenetic protein signaling pathways. 2609 86

Small leucine-rich proteoglycans, such as biglycan, and their side chain sulfated glycosaminoglycans (GAGs), have been suggested to be involved in bone formation and mineralization processes. The present study was designed to investigate whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures coupled with bone morphogenetic protein-4 (BMP-4) alter the differentiation and subsequent mineralization of MC3T3-E1 osteoblastic cells. CS-E, one of the oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP) activity, collagen deposition, and mineralization whereas heparin enhanced only ALP activity and mineralization. As well as CS-E, CS-H, and CPS also enhanced the mineralization of the cells. CS-E enhanced the mineralization of the cells by interacting with protein in the conditioned medium. CS-E induced mineralization was significantly inhibited by an antibody against BMP-4. The addition of exogenous BMP-4 further increased the capacity of CS-E to enhance mineralization. Fluorescence correlation spectroscopy method using fluoresceinamine-labeled GAG revealed that the oversulfated GAGs have a high affinity for BMP-4. The disaccharide analysis of the cells indicated that MC3T3-E1 cells are capable of producing oversulfated structures of CS by themselves. The lack of CS from the cells after chondroitinase treatment resulted in the inhibition of mineralization. These results in the present study indicate that oversulfated CS, which possesses 4,6-disulfates in N-acetyl-galactosamine, binds to BMP-4 and promotes osteoblast differentiation and subsequent mineralization.
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PMID:Oversulfated chondroitin sulfate-E binds to BMP-4 and enhances osteoblast differentiation. 1872 Mar 84


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