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

Abstract

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 *

Survey of the year 2004 commercial optical biosensor literature

“…Of the 678 articles that stated which Biacore platform was used, most utilized 2000 and 3000 platforms [222, (33%) and 249 (37%), respectively]. Investigators also reported data obtained from Biacore X (129, 19%) and 1000 (57, 8%), as well as from S51 [273,818,831,843,865], J [223,285,737,745,759], Q [892,905,907,910,913], Bialite [492,726,787,873] and Probe [348] platforms.…”

Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes

“…During chain elongation in the biosynthesis of CS/DS, the disaccharide units are modified by specific sulfotransferases at C-2 of GlcA/IdoA, and C-4 and/or C-6 of GalNAc in various combinations, and display enormous structural diversity producing characteristic sulfation patterns critical 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 as a dramatic increase in the proportion of IdoA(2-O-sulfate)-GalNAc(4-O-sulfate) units in the cerebellum [9]. The proportion of oversulfated disaccharides and the presence of IdoA are crucial factors for the neurite outgrowth-promoting (NOP) activity of CS/DS [10][11][12][13][14]. CS/DS chains from embryonic pig brains contain a higher proportion of IdoA than those prepared from adult pig brains [12].…”

Demonstration of the hepatocyte growth factor signaling pathway in the in vitro neuritogenic activity of chondroitin sulfate from ray fish cartilage

“…The average molecular size of ray cartilage CS and shark cartilage CS-C was determined to be 142 and 123 kDa, respectively, larger than that of the CS chains from other sources including embryonic pig brain (40 kDa) [10], shark skin (70 kDa) [11], shark liver (76 kDa) [15], and hagfish notochord (18 kDa) [12]. Although the two had similar structural features, the ray cartilage CS displayed higher NOP activity than shark cartilage CS-C, suggesting that the CS chains from ray cartilage contain a specific saccharide sequence required for interaction with growth/neurotrophic factors.…”

“…Several studies have shown that the sulfation pattern of CS in the brain alters during development, characterized by an increase in 4-O-sulfation and a decrease in 6-O-sulfation [5,6]. The proportion of oversulfated disaccharide units, GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate) and GlcUA-GalNAc(4,6-O-disulfate), has been demonstrated to be crucial to the neurite outgrowth-promoting (NOP) activity of CS [7][8][9][10][11][12][13]. The NOP activity toward embryonic mouse hippocampal neurons of mouse brain CS/DS and shark cartilage CS/DS, which contains a high proportion of the GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate) unit [13], has been verified to be executed by capturing endogenous growth/neurotrophic factors produced by non-neuronal cells (glial cells), and then presenting them to neuronal cells [4,14,15].…”