Oversulfated Dermatan Sulfate Exhibits Neurite Outgrowth-promoting Activity toward Embryonic Mouse Hippocampal Neurons

Hikino, Megumi; Mikami, Tadahisa; Faissner, Andréas; Vilela-Silva, Ana-Cristina E.S.; Pavão, Mauro S. G.; Sugahara, Kazuyuki

doi:10.1074/jbc.m308169200

Cited by 120 publications

(130 citation statements)

References 66 publications

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“…Analysis of the data was also carried out by enumerating the number of primary neurites/cell for 100 randomly selected cells, and the results show that the neuronal cells cultured on the CS-H substratum had, on average, 1.5 neurites/ cell compared with 3 or 1.9 neurites observed for cells grown on the substratum coated with poly-DL-ornithine alone or CS-E, respectively (Fig. 3D), which is in contrast to the formation of multiple dendritic neurites in addition to a single axonic neurite observed for the CS-H preparation eluted at 3.0 M NaCl from a Dowex column (14), which contained almost exclusively IdoUA and little GlcUA (23).…”

Section: Determination Of the Molecular Mass Of Cs-h-mentioning

confidence: 80%

“…8A and Table III). Thus, the CS-H preparation used in this and a previous study (14), which was eluted from a Dowex column with 2.0 and 3.0 M NaCl, had a sulfate/disaccharide ratio of 1.43 and 1.68, respectively.…”

Section: Specific Interactions Of the Cs-h Preparation With Neurotropmentioning

confidence: 96%

“…Neurite Outgrowth Promotion Assay-The neurite outgrowth-promoting activity of the purified CS-H preparation was assayed as reported previously (14). Briefly, the CS-H preparation (0.7 g as uronic acid) or an equivalent amount of its digest with chondroitinase ABC, B, or AC-I diluted with phosphate-buffered saline was coated on plastic coverslips, which had been precoated with poly-DL-ornithine at 37°C overnight.…”

Section: Determination Of the Digestibility Of The Purified Cs-h Prepmentioning

confidence: 99%

“…Neuritogenic activities were shown for various IdoUA-rich oversulfated DS chains from marine animals (14), and not only neuritogenic but also growth factor binding properties were revealed for the CS/DS hybrid chains attached to phosphacan/ DSD-1-PG from neonatal mouse brains (14,15) and for the free hybrid chains isolated from embryonic pig brains (16), both of which contain an appreciable proportion of functional IdoUA.…”

mentioning

confidence: 99%

“…Notochord is a connective tissue that supports the neural tube and that induces the formation of the central nervous system during the development of vertebrates. CS-H contains the characteristic oversulfated units IdoUA␣1-3GalNAc(4S,6S) and IdoUA(2S)␣1-3GalNAc(4S,6S), where 2S, 4S, and 6S represent sulfate at C-2, C-4, and C-6, respectively (22,23), hence regarded as DS, and exhibits axonic and dendritic neuritogenic activities for mouse hippocampal neurons (14). In view of the importance of the hybrid nature of the functional mammalian CS/DS chains in mouse (14,15) and pig (16) brains, we searched for CS/DS hybrid chains in CS-H and demonstrated axonic neuritogenic and binding activities for a number of growth factors and a few major neurotrophic factors expressed in the brain.…”

mentioning

confidence: 99%

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Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

Nandini

Mikami

Ohta

et al. 2004

Journal of Biological Chemistry

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115

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Pivotal functions of glycosaminoglycan (GAG) 1 side chains of proteoglycans (PGs), especially heparan sulfate (HS), have been implicated in biological processes such as cell adhesion, proliferation, and differentiation and tissue morphogenesis (1). Chondroitin sulfate (CS) and dermatan sulfate (DS) are also found ubiquitously in the extracellular matrices and at cell surfaces, being main components of cartilage and skin, respectively. CS consists of repeating disaccharide units of -4Gl-cUA␤1-3GalNAc␤1-, whereas DS is an isomeric form of CS and is formed from precursor CS through the action of glucuronyl C5 epimerase, thus consisting of disaccharide units of -4Gl-cUA␤1-3GalNAc␤1-and -4IdoUA␣1-3GalNAc␤1-in varying proportions (2). These disaccharide units are modified during chain elongation by specific sulfotransferases at C-2 of GlcUA/ IdoUA and/or C-4 and/or C-6 of GalNAc in various combinations, producing characteristic sulfation patterns critical for binding to various functional proteins displaying enormous structural diversity, comparable with that of HS, by embedding multiple overlapping functional sequences (3). Sulfation profiles of GAGs change during development (4, 5). Growing evidence indicates the involvement of CS and DS in the signaling of various heparin-binding growth factors and cytokines (6 -8).We and others have shown the importance of this class of molecule, from simple chondroitin involved in cell division of a nematode (9) to differentially oversulfated CS-D and CS-E involved in neuroregulatory functions (10 -12) and the binding of growth factors in mammalian systems (13). While pursuing the critical structural elements in the CS variants, we became *

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Section: Determination Of the Molecular Mass Of Cs-h-mentioning

confidence: 80%

Section: Specific Interactions Of the Cs-h Preparation With Neurotropmentioning

confidence: 96%

Section: Determination Of the Digestibility Of The Purified Cs-h Prepmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

Nandini

Mikami

Ohta

et al. 2004

Journal of Biological Chemistry

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115

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Alginate Sulfate Substrates Control Growth Factor Binding and Growth of Primary Neurons: Toward Engineered 3D Neural Networks

et al. 2020

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Sulfated glycosaminoglycans (sGAGs) are vital molecules of the extracellular matrix (ECM) of the nervous system known to regulate proliferation, migration, and differentiation of neurons mainly through binding relevant growth factors. Alginate sulfate (AlgSulf) mimics sGAGs and binds growth factors such as basic fibroblast growth factor (FGF‐2). Here, thin films of biotinylated AlgSulf (b‐AlgSulfn) are engineered with sulfation degrees (DS = 0.0 and 2.7) and the effect of polysaccharide concentration on FGF‐2 and nerve growth factor (β‐NGF) binding and subsequent primary neural viability and neurite outgrowth is assessed. An increase in b‐AlgSulfn concentration results in higher FGF‐2 and β‐NGF binding as demonstrated by greater frequency and dissipation shifts measured with quartz crystal microbalance with dissipation monitoring (QCM‐D). Primary neurons seeded on the 2D b‐AlgSulfn films maintain high viability comparable to positive controls grown on poly‐d‐lysine. Neurons grown in 3D AlgSulf hydrogels (DS = 0.8) exhibit a significantly higher viability, neurite numbers and mean branch length compared to neurons grown in nonsulfated controls. Finally, a first step is made toward constructing 3D neuronal networks by controllably patterning neurons encapsulated in AlgSulf into an alginate carrier. The substrates and neural networks developed in the current study can be used in basic and applied neural applications.

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Engineered Sulfated Polysaccharides for Biomedical Applications

Arlov

Rütsche

Korayem

et al. 2021

Adv Funct Materials

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Sulfated polysaccharides are ubiquitous in living systems and have central roles in biological functions such as organism development, cell proliferation and differentiation, cellular communication, tissue homeostasis, and host defense. Engineered sulfated polysaccharides (ESPs) are structural derivatives not found in nature but generated through chemical and enzymatic modification of natural polysaccharides, as well as chemically synthesized oligo‐ and polysaccharides. ESPs exhibit novel and augmented biological properties compared with their unmodified counterparts, mainly through facilitating interactions with other macromolecules. These interactions are closely linked to their sulfation patterns and backbone structures, providing a means to fine‐tune biological properties and characterize structural–functional relationships by employing well‐characterized polysaccharides and strategies for regioselective modification. The following review provides a comprehensive overview of the synthesis and characterization of ESPs and of their biological properties. Through the pioneering research presented here, key emerging application areas for ESPs, which can lead to novel breakthroughs in biomedical research and clinical treatments, are highlighted.

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Oversulfated Dermatan Sulfate Exhibits Neurite Outgrowth-promoting Activity toward Embryonic Mouse Hippocampal Neurons

Cited by 120 publications

References 66 publications

Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

Alginate Sulfate Substrates Control Growth Factor Binding and Growth of Primary Neurons: Toward Engineered 3D Neural Networks

Engineered Sulfated Polysaccharides for Biomedical Applications

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