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 immunoregulatory effect of Catrix on in vitro and and in vivo antibody production was examined in mice. Catrix, an acidic mucopolysaccharide complex, contains glycosaminoglycans including chondroitin sulfate. Catrix-S, a soluble derivative, was found to enhance T-dependent and T-independent antibody responses in vivo in a dose-dependent manner, with 100 mg intraperitoneally or 10 mg intravenously being optimal. Lower doses were found to be less effective or inhibitory. In vitro, the enhancing activity of Catrix-S on proliferative response was additive with that of dextran sulfate and lipopolysaccharide but not with chondroitin sulfate C. This immunoaugmenting activity appears to be related to the chondroitin sulfate component of Catrix-S, because both have similar effects on in vivo and in vitro antibody responses and because chondroitinase ABC inactivates activity. The inhibitory activity of Catrix-S could be separated from its stimulatory effects by ammonium sulfate precipitation or by fractionation according to molecular weight. The immunoaugmenting effect was present in the 0-30% saturated ammonium sulfate precipitate and in the 5-10,000-m.w. and 30-100,000-m.w. fractions. The ability of Catrix-S to enhance antibody responses in nude as well as in normal mice, and antibody responses to T-independent as well as to T-dependent antigens, indicates that its activity is due in part to a direct effect on B cells and/or to an indirect effect mediated by macrophages.
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PMID:Immunoregulatory effects of catrix. 284 89

The production of chicken myelomonocytic growth factor (cMGF) can be rapidly induced by bacterial lipopolysaccharide from the macrophage cell line HD11. Immunoprecipitation analysis of lipopolysaccharide-induced HD11 cells labeled with various radioactive precursors showed the secretion of a variety of cMGF forms. The precursor-product relationships of the different cMGF forms were studied by pulse-chase experiments, by long-term metabolic labeling in the presence or absence of glycosylation- and oligosaccharide-processing inhibitors, as well as by glycosidase treatment of immunoprecipitates. Our results show that the half-time for intracellular processing/secretion is less than 10 min, making cMGF one of the most rapidly processed proteins. The different forms of the factor are generated from a 24-kDa polypeptide precursor by co- and post-translational acquisition of one or two N-linked oligosaccharides and by O-linked glycosylation. In addition, a fraction of cMGF is modified by long chain, chondroitinase-sensitive, sulfated glycans. This modification is tunicamycin-sensitive, suggesting that the sulfated glycans are attached to N-linked rather than to O-linked oligosaccharides.
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PMID:Hematopoietic growth factor glycosylation. Multiple forms of chicken myelomonocytic growth factor. 327 26

Plasminogen activator inhibitor-1 (PAI-1) is a primary endogenous inhibitor of tissue-type plasminogen activator (t-PA). In this study, we examined the effects of oversulfated fucoidan (OSF) derivatives and heparin on lipopolysaccharide (LPS)-induced release of PAI-1 antigen from cultured human umbilical vein endothelial cells (HUVEC). Addition of LPS (10 micrograms/ml) enhanced the release of PAI-1 by HUVEC but not of t-PA antigen. At 18 h, a 2.4-fold increase in the extracellular PAI-1 level was observed. The increased PAI-1 level was reduced to control level by the simultaneous addition of 10 micrograms/ml of OSF or heparin. The suppressive effect of native fucoidan was negligible. We also examined the molecular size effect of OSF, using 10-20, 20-40, and 40-60 kDa fragments. The result indicated that these fragments were effective as well as the 100-130 kDa form of OSF, hence suggesting an important role of the degree of sulfation. Interleukin-1 beta (IL-1 beta) is a potent inducer of PAI-1 in cultured HUVEC. Heparin, OSF, and its fragments did not suppress the IL-1 beta-induced release of PAI-1 antigen. Treatment of HUVEC with heparitinase or monoclonal antibody against heparin sulfate proteoglycan (HSPG) resulted in a complete loss of its ability to enhance PAI-1 release in response to LPS stimulation, while the chondroitinase ABC treatment hardly affected the PAI-1 production. These results suggest that HSPG is involved in the initial binding of LPS to HUVEC. The suppressive effects of OSF and heparin on LPS-induced PAI-1 release may result from the inhibition of LPS binding to the cell surface HSPG.
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PMID:Oversulfated fucoidan and heparin suppress endotoxin induction of plasminogen activator inhibitor-1 in cultured human endothelial cells: their possible mechanism of action. 757 76

Mixtures of hyaluronan (HA), chondroitin sulfate (CS)-A and CS-C oligosaccharides were generated through the enzymatic digestion of the polysaccharides with either mammalian hyaluronidase or bacterial HA lyase or chondroitinase. Compared to mammalian enzymes, bacterial enzymes hydrolyze the polysaccharides through a different mechanism yielding chemically distinct sets of oligosaccharides. Peripheral leukocytes and a human monocytic cell line were exposed to these oligosaccharides and the amount of interleukin-12 released by the cells was measured. For all types of oligosaccharide tested, we found that the amount of interleukin-12 induced by oligosaccharides generated with bacterial enzyme was significantly lower than the amount of interleukin-12 induced by oligosaccharides generated with mammalian enzyme. In addition, we observed that CS oligosaccharides generated with bacterial enzyme were capable of reducing the lipopolysaccharide-induced interleukin-12 production in macrophages. Our results indicate that HA or CS oligosaccharides generated with mammalian enzymes might possess pro-inflammatory potential, while HA or CS oligosaccharides generated with bacterial enzymes might possess non- or anti-inflammatory properties. The implications of our findings in view of the ongoing investigation of the potential therapeutic benefits of HA and CS in arthritis or other inflammatory pathologies are discussed.
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PMID:Interleukin-12 release from macrophages by hyaluronan, chondroitin sulfate A and chondroitin sulfate C oligosaccharides. 1455 66

The appearance of a high molecular weight gelatinolytic enzyme (230 kDa) correlated with cartilage collagen loss in chick embryonic tibias cultured with lipopolysaccharide. This 230 kDa enzyme was purified and its activity was measured on synthetic and natural substrates. The enzyme was activated by aminophenylmercuric acetate and inhibited by ethylenediaminetetraacetic acid, phenanthroline, marimastat or tissue inhibitors of metalloproteinases. Amino acid sequences of peptides derived from the purified enzyme showed identity with avian MMP-9. Digestion of the intact enzyme with chondroitinase decreased the size of the molecule to 80 kDa on SDS-PAGE. When chick embryonic tibia cultures were radiolabeled with (35)S-sulfate, the radiolabel co-purified with the 230 kDa gelatinase. Chondroitinase treated 230 kDa gelatinase also reacted with specific anti-chondroitin sulfate antibodies and FACE analysis revealed a predominance of chondroitin-4-sulfate. These results demonstrate this avian matrix metalloproteinase contained glycosaminoglycan chains. To our knowledge, this is the first report of a matrix metalloproteinase in a proteoglycan form.
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PMID:Matrix metalloproteinase-9 in a unique proteoglycan form in avian embryonic growth plate cartilage. 2234 60