Chondroitin sulfate of appican, the proteoglycan form of amyloid precursor protein, produced by C6 glioma cells interacts with heparin‐binding neuroregulatory factors

Umehara, Yuko; Yamada, Shuhei; Nishimura, Shuji; Shioi, Junichi; Robakis, Nikolaos K.; Sugahara, Kazuyuki

doi:10.1016/s0014-5793(03)01506-0

Cited by 31 publications

(19 citation statements)

References 34 publications

(54 reference statements)

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“…Interestingly, however, the CS chains on syndecan-1, with an E-unit content comparable with that of syndecan-4, bound MK and PTN with much lower affinity, suggesting that the sequence is more important for the binding of these growth factors than the E-unit content. Our previous studies demonstrated that CS chains with an E-unit content of 14% from appican (43), a CS-PG form of amyloid precursor protein, strongly bind bFGF, MK, and PTN, and the E unit is essential for the binding (38). Hence, the lack of binding of bFGF to CS/syndecan-4 with an E-unit content of 9% suggests that the sequential arrangement of an E-unit with either an A-and/or C-unit in the CS chains is essential for binding the growth factor.…”

Section: Discussionmentioning

confidence: 99%

“…Biotinylation of Syndecan-1 and -4 Ectodomains-Biotinylation of the primary amines in the core protein of syndecan-1 (3 g) and syndecan-4 (0.6 g as core protein) was carried out using EZ-link sulfo-NHS-LC-biotin, as described previously (38). For the preparation of biotinylated syndecan-1 or -4 ectodomains with HS chains (HS/syndecan-1 or -4), one-third of the biotinylated syndecan-1 or -4 ecodomains was treated with a protease-free preparation of CSase ABC (2 mIU) as described above.…”

Section: Disaccharide Composition Analysis Of Hs and Cs Chains From Smentioning

confidence: 99%

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Chondroitin Sulfate Chains on Syndecan-1 and Syndecan-4 from Normal Murine Mammary Gland Epithelial Cells Are Structurally and Functionally Distinct and Cooperate with Heparan Sulfate Chains to Bind Growth Factors

Deepa

Yamada

Zako

et al. 2004

Journal of Biological Chemistry

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167

128

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A comparative analysis was carried out of heparan sulfate (HS) and chondroitin sulfate (CS) chains of the ectodomains of hybrid type transmembrane proteoglycans, syndecan-1 and -4, synthesized simultaneously by normal murine mammary gland epithelial cells. Although the HS chains were structurally indistinguishable, intriguingly the CS chains were structurally and functionally distinct, probably reflecting the differential regulation of sulfotransferases involved in the synthesis of HS and CS. The CS chains of the two syndecans comprised nonsulfated, 4-O-, 6-O-, and 4,6-O-disulfated N-acetylgalactosamine-containing disaccharide units and were significantly different, with a higher degree of sulfation for syndecan-4. Functional analysis using a BIAcore system showed that basic fibroblast growth factor (bFGF) specifically bound only to the HS chains of both syndecans, whereas midkine (MK) and pleiotrophin (PTN) bound not only to the HS but also to the CS chains. Stronger binding of MK and PTN to the CS chains of syndecan-4 than those of syndecan-1 was revealed, supporting the structural and functional differences. Intriguingly, removal of the CS chains decreased the association and dissociation rate constants of MK, PTN, and bFGF for both syndecans, suggesting the simultaneous binding of these growth factors to both types of chains, producing a ternary complex that transfers the growth factors to the corresponding cell surface receptors more efficiently compared with the HS chains alone. The involvement of the core protein was also shown in the binding of MK and PTN to syndecan-1, suggesting the possibility of cooperation with the HS and/or CS chains in the binding of these growth factors and their delivery to the cell surface receptors. Proteoglycans (PG) 1 bear glycosaminoglycans (GAGs) such as heparan sulfate (HS) and chondroitin sulfate (CS). The repeating disaccharide unit in the HS and CS backbones isGlcUA/IdceA-GlcNAc and GlcUA-GalNAc, respectively, onto which are superimposed specific modification patterns, most notably the addition of sulfate groups by a variety of sulfotransferases (1). PGs are distributed ubiquitously in extracellular matrices and at cell surfaces (2). Syndecans are the major cell surface PGs expressed by virtually all epithelial cells. Four kinds of syndecans form a gene family, the transmembrane and cytoplasmic domain being conserved among all of the members (3-7). These syndecans are expressed with different cell-, tissue-, and developmental stage-specific patterns (8, 9), suggesting distinct functions for each family member (10), although some shared activities have been observed, for example, for syndecan-1 and -4 (3, 5, 11, 12).The majority of GAG chains added to the core proteins of syndecans are of the HS type, although syndecan-1 (13) and syndecan-4 (14) are modified by CS chains as well. The HS chains bind collagen types I, III, and V (15), fibronectin (16), tenascin (17), thrombospondin (18) and basic fibroblast growth factor (bFGF) (19,20), and other components of the cellula...

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Section: Discussionmentioning

confidence: 99%

Section: Disaccharide Composition Analysis Of Hs and Cs Chains From Smentioning

confidence: 99%

Chondroitin Sulfate Chains on Syndecan-1 and Syndecan-4 from Normal Murine Mammary Gland Epithelial Cells Are Structurally and Functionally Distinct and Cooperate with Heparan Sulfate Chains to Bind Growth Factors

Deepa

Yamada

Zako

et al. 2004

Journal of Biological Chemistry

Self Cite

167

128

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“…Our dissolving microneedles were made of water-soluble thread-forming polymer, chondroitin sulfate and dextran. Chondroitin sulfate is a peptideglycan that exists in biological tissues (67)(68)(69)(70)(71)(72). Both chondroitin sulfate and dextran are used as an injection preparation.…”

Section: Safety Of Dissolving Microneedlesmentioning

confidence: 99%

Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats

et al. 2010

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“…This simple repeat structure undergoes extensive variable modification by sulfation at the C2 or C3 position of D-glucuronic acid residues and/or the C4 or C6 position of N-acetyl-D-galactosamine residues during biosynthesis (Umehara et al 2004).…”

mentioning

confidence: 99%

Evaluation of Chondroitin Sulfate Bioactivity in Hippocampal Neurones and the Astrocyte Cell Line U373: Influence of Position of Sulfate Groups and Charge Density

Rapp

Brandl

Volpi³

et al. 2005

Basic Clin Pharma Tox

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Chondroitin sulfates are linear polysaccharides of alternating glucuronic acid and N-acetylgalactosamine, sulfated in varying positions. They form the extracellular framework providing the information for the structural establishment of tissues in multicellular organisms. Growth cones of neurones modulate their outgrowth according to signals received from proteoglycans. The exact molecular structures behind these functions are not fully understood, but structural details of the carbohydrate backbone are crucial. In this report we have employed quantitative cytometry on hippocampal neurite outgrowth in the presence of chondroitin sulfate added in solution to determine the influence of the position and density of the sulfate groups of the N-acetyl-D-galactosamine-residues of chondroitin sulfates. It is of profound interest whether externally added chondroitin sulfates can compete with core protein bound chondroitin sulfate to modulate the effects of tissue-synthesized matrix. In series of microscopic images 3 parameters of neuritic outgrowth activity, neurite length, number of neurites and fasciculation (thickness of neurites) are analyzed at concentrations occurring in intact tissues. Fasciculation increased and number of neurites decreased with high di-sulfation. No significant differences on process length reduction were found between the isotypes. Specificity of effects found is emphasized, as no influence on cell proliferation with U373 human astrocyte cell line is detectable, while neurones clearly are inhibited. The IC 30 and IC 50 values of chondroitin sulfates isoforms are presented for neurones. The data indicate that the soluble fragments from chondroitin sulfate are actively modulating cell development. Besides dosage, sulfation density and position are relevant for effects of chondroitin sulfate in neuronal regenerative activity.Chondroitin sulfate glycosaminoglycans are complex sulfated polysaccharides with a backbone structure composed of a repeating disaccharide building units of 4D-glucuronic acid-b1-3N-acetyl-D-galactosamine-b1. This simple repeat structure undergoes extensive variable modification by sulfation at the C2 or C3 position of D-glucuronic acid residues and/or the C4 or C6 position of N-acetyl-D-galactosamine residues during biosynthesis (Umehara et al. 2004).Diversity in sulfation results in structural variability of chondroitin sulfate chains, which is the basis for their functional diversity. Oversulfated chondroitin sulfate variants chondroitin sulfate-D and chondroitin sulfate-E under certain conditions promote neurite outgrowth, and are characterized by peculiar disulfated disaccharide motifs including D-glucuronic acid -(2-O-sulfate) b1-4N-acetyl-D-galactosamine(6-O-sulfate), or D-glucuronic acid-b1-3N-acetyl-D-galactosamine(4,6-O-disulfate), in chondroitin sulfate-D or chondroitin sulfate-E, respectively.Chondroitin sulfate proteoglycans assist in the structural establishment of tissues in multicellular organisms. They build a stabilized molecular framework and by sp...

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Chondroitin sulfate of appican, the proteoglycan form of amyloid precursor protein, produced by C6 glioma cells interacts with heparin‐binding neuroregulatory factors

Cited by 31 publications

References 34 publications

Chondroitin Sulfate Chains on Syndecan-1 and Syndecan-4 from Normal Murine Mammary Gland Epithelial Cells Are Structurally and Functionally Distinct and Cooperate with Heparan Sulfate Chains to Bind Growth Factors

Chondroitin Sulfate Chains on Syndecan-1 and Syndecan-4 from Normal Murine Mammary Gland Epithelial Cells Are Structurally and Functionally Distinct and Cooperate with Heparan Sulfate Chains to Bind Growth Factors

Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats

Evaluation of Chondroitin Sulfate Bioactivity in Hippocampal Neurones and the Astrocyte Cell Line U373: Influence of Position of Sulfate Groups and Charge Density

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