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Kazuyuki Sugahara - One of the best experts on this subject based on the ideXlab platform.
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recent advances in the structural biology of Chondroitin sulfate and dermatan sulfate
Current Opinion in Structural Biology, 2003Co-Authors: Kazuyuki Sugahara, Toru Uyama, Tadahisa Mikami, Souhei Mizuguchi, Kazuya Nomura, Hiroshi KitagawaAbstract:Recent glycobiology studies have suggested fundamental biological functions for Chondroitin, Chondroitin sulfate and dermatan sulfate, which are widely distributed as glycosaminoglycan sidechains of proteoglycans in the extracellular matrix and at cell surfaces. They have been implicated in the signaling functions of various heparin-binding growth factors and chemokines, and play critical roles in the development of the central nervous system. They also function as receptors for various pathogens. These functions are closely associated with the sulfation patterns of the glycosaminoglycan chains. Surprisingly, nonsulfated Chondroitin is indispensable in the morphogenesis and cell division of Caenorhabditis elegans, as revealed by RNA interference experiments of the recently cloned Chondroitin synthase gene and by the analysis of mutants of squashed vulva genes.
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heterogeneity of the Chondroitin sulfate portion of phosphacan 6b4 proteoglycan regulates its binding affinity for pleiotrophin heparin binding growth associated molecule
Journal of Biological Chemistry, 2003Co-Authors: Nobuaki Maeda, Kazuyuki Sugahara, Yuki Yajima, Tadahisa Mikami, Tomio YabeAbstract:Abstract PTPζ is a receptor-type protein-tyrosine phosphatase that is synthesized as a Chondroitin sulfate proteoglycan and uses pleiotrophin as a ligand. The Chondroitin sulfate portion of this receptor is essential for high affinity binding to pleiotrophin. Here, we purified phosphacan, which corresponds to the extracellular domain of PTPζ, from postnatal day 7 (P7) and P12 rat cerebral cortex (PG-P7 and PG-P12, respectively) and from P20 rat whole brain (PG-P20). The Chondroitin sulfate of these preparations displayed immunologically and compositionally different structures. In particular, only PG-P20 reacted with the monoclonal antibody MO-225, which recognizes Chondroitin sulfate containing the GlcA(2S)β1–3GalNAc(6S) disaccharide unit (D unit). Analysis of the Chondroitinase digestion products revealed that GlcAβ1–3GalNAc(4S) disaccharide unit (A unit) was the major component in these preparations and that PG-P20 contained 1.3% D unit, which was not detected in PG-P7 and PG-P12. Interaction analysis using a surface plasmon resonance biosensor indicated that PG-P20 had ∼5-fold stronger affinity for pleiotrophin (dissociation constant (KD) = 0.14 nm) than PG-P7 and PG-P12, although all these preparations showed similar low affinity binding to pleiotrophin after Chondroitinase ABC digestion (KD = 1.4 ∼ 1.6 nm). We also found that shark cartilage Chondroitin sulfate D containing ∼20% D unit bound to pleiotrophin with moderate affinity (KD = 2.7 nm), whereas whale cartilage Chondroitin sulfate A showed no binding to this growth factor. These results suggest that variation of Chondroitin sulfate plays important roles in the regulation of signal transduction in the brain.
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heterogeneity of the Chondroitin sulfate portion of phosphacan 6b4 proteoglycan regulates its binding affinity for pleiotrophin heparin binding growth associated molecule
Journal of Biological Chemistry, 2003Co-Authors: Nobuaki Maeda, Kazuyuki Sugahara, Yuki Yajima, Tadahisa Mikami, Tomio YabeAbstract:PTP zeta is a receptor-type protein-tyrosine phosphatase that is synthesized as a Chondroitin sulfate proteoglycan and uses pleiotrophin as a ligand. The Chondroitin sulfate portion of this receptor is essential for high affinity binding to pleiotrophin. Here, we purified phosphacan, which corresponds to the extracellular domain of PTP zeta, from postnatal day 7 (P7) and P12 rat cerebral cortex (PG-P7 and PG-P12, respectively) and from P20 rat whole brain (PG-P20). The Chondroitin sulfate of these preparations displayed immunologically and compositionally different structures. In particular, only PG-P20 reacted with the monoclonal antibody MO-225, which recognizes Chondroitin sulfate containing the GlcA(2S)beta 1-3GalNAc(6S) disaccharide unit (D unit). Analysis of the Chondroitinase digestion products revealed that GlcA beta 1-3GalNAc(4S) disaccharide unit (A unit) was the major component in these preparations and that PG-P20 contained 1.3% D unit, which was not detected in PG-P7 and PG-P12. Interaction analysis using a surface plasmon resonance biosensor indicated that PG-P20 had approximately 5-fold stronger affinity for pleiotrophin (dissociation constant (KD) = 0.14 nM) than PG-P7 and PG-P12, although all these preparations showed similar low affinity binding to pleiotrophin after Chondroitinase ABC digestion (KD = 1.4 approximately 1.6 nM). We also found that shark cartilage Chondroitin sulfate D containing approximately 20% D unit bound to pleiotrophin with moderate affinity (KD = 2.7 nM), whereas whale cartilage Chondroitin sulfate A showed no binding to this growth factor. These results suggest that variation of Chondroitin sulfate plays important roles in the regulation of signal transduction in the brain.
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Chondroitin proteoglycans are involved in cell division of caenorhabditis elegans
Nature, 2003Co-Authors: Souhei Mizuguchi, Toru Uyama, Hiroshi Kitagawa, Kazuyuki Sugahara, Kazuko H Nomura, Katsufumi Dejima, Keiko Gengyoando, Shohei Mitani, Kazuya NomuraAbstract:Glycosaminoglycans such as heparan sulphate and Chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impairs developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways, but little is known about the involvement of Chondroitin. Undersulphated and oversulphated Chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development. To investigate Chondroitin functions, we cloned a Chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking Chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in Chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that Chondroitin is required for embryonic cytokinesis and cell division.
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molecular cloning and expression of a second Chondroitin n acetylgalactosaminyltransferase involved in the initiation and elongation of Chondroitin dermatan sulfate
Journal of Biological Chemistry, 2003Co-Authors: Toru Uyama, Hiroshi Kitagawa, Junichi Tamura, Junko Tanaka, Tomoya Ogawa, Kazuyuki SugaharaAbstract:We identified a novel human ChondroitinN-acetylgalactosaminyltransferase, designated Chondroitin GalNAcT-2 after a BLAST analysis of the GenBankTM data base using the sequence of a previously described human ChondroitinN-acetylgalactosaminyltransferase (Chondroitin GalNAcT-1) as a probe. The new cDNA sequence contained an open reading frame encoding a protein of 542 amino acids with a type II transmembrane protein topology. The amino acid sequence displayed 60% identity to that of human Chondroitin GalNAcT-1. Like Chondroitin GalNAcT-1, the expression of a soluble form of the protein in COS-1 cells produced an active enzyme, which not only transferred β1,4-N-acetylgalactosamine (GalNAc) from UDP-[3H]GalNAc to a polymer Chondroitin representing growing Chondroitin chains (β-GalNAc transferase II activity) but also to GlcUAβ1–3Galβ1-O-C2H4NHCbz, a synthetic substrate for β-GalNAc transferase I that transfers the first GalNAc to the core tetrasaccharide in the protein-linkage region of Chondroitin sulfate. In contrast, the tetrasaccharide serine (GlcUAβ1–3Galβ1–3Galβ1–4Xylβ1-O-Ser) derived from the linkage region, which is an inert acceptor substrate for Chondroitin GalNAcT-1, served as an acceptor substrate. The coding region of this enzyme was divided into seven discrete exons, which is similar to the genomic organization of the Chondroitin GalNAcT-1 gene, and was localized to chromosome 10q11.22. Northern blot analysis revealed that the Chondroitin GalNAcT-2 gene exhibited a ubiquitous but differing expression in human tissues, and the expression pattern differed from that of Chondroitin GalNAcT-1. Thus, we demonstrated redundancy in the Chondroitin GalNAc transferases involved in the biosynthetic initiation and elongation of Chondroitin sulfate, which is important for understanding the biosynthetic mechanisms leading to the selective chain assembly of Chondroitin/dermatan sulfate on the linkage region tetrasaccharide common to various proteoglycans containing Chondroitin/dermatan sulfate and heparin/heparan sulfate chains.
Stuart B. Hooper - One of the best experts on this subject based on the ideXlab platform.
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glucocorticoids influence versican and Chondroitin sulphate proteoglycan levels in the fetal sheep lung
Respiratory Research, 2018Co-Authors: Annie R. A. Mcdougall, Amanda J. Fosang, Jessica Faggian, Megan J. Wallace, Kelly J. Crossley, Timothy J. Cole, Stuart B. HooperAbstract:Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of Chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Lung tissue was collected from 1) fetal sheep at 131 ± 0.1 days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2 × 11.4 mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4 ± 0.7 AU, compared with saline-infused fetuses (18.9 ± 0.7 AU: p = 0.04) but did not significantly alter the level of versican or Chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2 ± 2.2 AU), compared with sham-operated fetuses (17.8 ± 2.0 AU; p = 0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2 ± 0.9 AU, 24.9 ± 1.4 AU and 23.2 ± 1.0 AU, respectively), compared with saline-exposed fetuses (24.3 ± 0.4 AU, p = 0.0004; 33.3±0.6 AU, p = 0.0003; 29.8±1.3 AU, 0.03, respectively). These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol.
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Glucocorticoids influence versican and Chondroitin sulphate proteoglycan levels in the fetal sheep lung
BMC, 2018Co-Authors: Annie R. A. Mcdougall, Amanda J. Fosang, Jessica Faggian, Megan J. Wallace, Kelly J. Crossley, Timothy J. Cole, Stuart B. HooperAbstract:Abstract Background Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of Chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Methods Lung tissue was collected from 1) fetal sheep at 131 ± 0.1 days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2 × 11.4 mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Results Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4 ± 0.7 AU, compared with saline-infused fetuses (18.9 ± 0.7 AU: p = 0.04) but did not significantly alter the level of versican or Chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2 ± 2.2 AU), compared with sham-operated fetuses (17.8 ± 2.0 AU; p = 0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2 ± 0.9 AU, 24.9 ± 1.4 AU and 23.2 ± 1.0 AU, respectively), compared with saline-exposed fetuses (24.3 ± 0.4 AU, p = 0.0004; 33.3±0.6 AU, p = 0.0003; 29.8±1.3 AU, 0.03, respectively). Conclusions These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol
Miroslaw Cygler - One of the best experts on this subject based on the ideXlab platform.
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high resolution crystal structure of arthrobacter aurescens Chondroitin ac lyase an enzyme substrate complex defines the catalytic mechanism
Journal of Molecular Biology, 2004Co-Authors: Valery V. Lunin, Hirofumi Miyazono, Takuji Kaneko, Mamoru Kyogashima, Yunge Li, Alexander W Bell, Robert J Linhardt, Miroslaw CyglerAbstract:Abstract Chondroitin lyases (EC 4.2.2.4 and EC 4.2.2.5) are glycosaminoglycan-degrading enzymes that act as eliminases. Chondroitin lyase AC from Arthrobacter aurescens (ArthroAC) is known to act on Chondroitin 4-sulfate and Chondroitin 6-sulfate but not on dermatan sulfate. Like other Chondroitin AC lyases, it is capable of cleaving hyaluronan. We have determined the three-dimensional crystal structure of ArthroAC in its native form as well as in complex with its substrates (Chondroitin 4-sulfate tetrasaccharide, CStetra and hyaluronan tetrasaccharide) at resolution varying from 1.25 A to 1.9 A. The primary sequence of ArthroAC has not been previously determined but it was possible to determine the amino acid sequence of this enzyme from the high-resolution electron density maps and to confirm it by mass spectrometry. The enzyme–substrate complexes were obtained by soaking the substrate into the crystals for varying lengths of time (30 seconds to ten hours) and flash-cooling the crystals. The electron density map for crystals soaked in the substrate for as short as 30 seconds showed the substrate clearly and indicated that the ring of central glucuronic acid assumes a distorted boat conformation. This structure strongly supports the lytic mechanism where Tyr242 acts as a general base that abstracts the proton from the C5 position of glucuronic acid while Asn183 and His233 neutralize the charge on the glucuronate acidic group. Comparison of this structure with that of Chondroitinase AC from Flavobacterium heparinum (FlavoAC) provides an explanation for the exolytic and endolytic mode of action of ArthroAC and FlavoAC, respectively.
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crystal structure of proteus vulgaris Chondroitin sulfate abc lyase i at 1 9a resolution
Journal of Molecular Biology, 2003Co-Authors: Weijun Huang, Hirofumi Miyazono, V V Lunin, Sakaru Suzuki, Nobuo Sugiura, Miroslaw CyglerAbstract:Abstract 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 β-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.
Sakaru Suzuki - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of proteus vulgaris Chondroitin sulfate abc lyase i at 1 9a resolution
Journal of Molecular Biology, 2003Co-Authors: Weijun Huang, Hirofumi Miyazono, V V Lunin, Sakaru Suzuki, Nobuo Sugiura, Miroslaw CyglerAbstract:Abstract 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 β-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.
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two distinct Chondroitin sulfate abc lyases an endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides
Journal of Biological Chemistry, 1997Co-Authors: Akio Hamai, Nobukazu Hashimoto, Hideo Mochizuki, Fumikazu Kato, Yoshitaka Makiguchi, Katsuyuki Horie, Sakaru SuzukiAbstract:Abstract Crude enzyme obtained from Chondroitin sulfate-induced Proteus vulgaris NCTC 4636 has been fractionated into 1) an endoeliminase capable of depolymerizing Chondroitin sulfate and related polysaccharides to produce, as end products, a mixture of Δ4-unsaturated tetra- and disaccharides and 2) an exoeliminase preferentially acting on Chondroitin sulfate tetra- and hexasaccharides to yield the respective disaccharides. Isolation of the two enzymes was achieved by a simple two-step procedure: extracting the enzymes from intact P. vulgaris cells with a buffer solution of nonionic surfactant and then treating the extract by cation-exchange chromatography. Each of the enzymes thus prepared was apparently homogeneous as assessed by SDS-polyacrylamide gel electrophoresis and readily crystallized from polyethylene glycol solutions. Both enzymes acted on various substrates such as Chondroitin sulfate, Chondroitin sulfate proteoglycan, and dermatan sulfate at high, but significantly different, initial rates. They also attacked hyaluronan but at far lower rates and were inactive to keratan sulfate, heparan sulfate, and heparin. Our results show that the known ability of the conventional enzyme called “Chondroitinase ABC” to catalyze the complete depolymerization of Chondroitin sulfates to unsaturated disaccharides may actually result from the combination reactions by endoeliminase (Chondroitin sulfate ABC endolyase) and exoeliminase (Chondroitin sulfate ABC exolyase).
Jessica Faggian - One of the best experts on this subject based on the ideXlab platform.
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glucocorticoids influence versican and Chondroitin sulphate proteoglycan levels in the fetal sheep lung
Respiratory Research, 2018Co-Authors: Annie R. A. Mcdougall, Amanda J. Fosang, Jessica Faggian, Megan J. Wallace, Kelly J. Crossley, Timothy J. Cole, Stuart B. HooperAbstract:Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of Chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Lung tissue was collected from 1) fetal sheep at 131 ± 0.1 days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2 × 11.4 mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4 ± 0.7 AU, compared with saline-infused fetuses (18.9 ± 0.7 AU: p = 0.04) but did not significantly alter the level of versican or Chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2 ± 2.2 AU), compared with sham-operated fetuses (17.8 ± 2.0 AU; p = 0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2 ± 0.9 AU, 24.9 ± 1.4 AU and 23.2 ± 1.0 AU, respectively), compared with saline-exposed fetuses (24.3 ± 0.4 AU, p = 0.0004; 33.3±0.6 AU, p = 0.0003; 29.8±1.3 AU, 0.03, respectively). These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol.
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Glucocorticoids influence versican and Chondroitin sulphate proteoglycan levels in the fetal sheep lung
BMC, 2018Co-Authors: Annie R. A. Mcdougall, Amanda J. Fosang, Jessica Faggian, Megan J. Wallace, Kelly J. Crossley, Timothy J. Cole, Stuart B. HooperAbstract:Abstract Background Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of Chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Methods Lung tissue was collected from 1) fetal sheep at 131 ± 0.1 days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2 × 11.4 mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Results Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4 ± 0.7 AU, compared with saline-infused fetuses (18.9 ± 0.7 AU: p = 0.04) but did not significantly alter the level of versican or Chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2 ± 2.2 AU), compared with sham-operated fetuses (17.8 ± 2.0 AU; p = 0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2 ± 0.9 AU, 24.9 ± 1.4 AU and 23.2 ± 1.0 AU, respectively), compared with saline-exposed fetuses (24.3 ± 0.4 AU, p = 0.0004; 33.3±0.6 AU, p = 0.0003; 29.8±1.3 AU, 0.03, respectively). Conclusions These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol