title: Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling.
abstract: Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates.
authors.affiliation: Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ramachandra
authors.forename: Ramesh B
authors.initials: RB
authors.lastname: Namburi
authors.forename: Olga
authors.initials: O
authors.lastname: Ortega-Martinez
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shi
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
authors.forename: Sam T
authors.initials: ST
authors.lastname: Dupont
authors.forename: Michael C
authors.initials: MC
authors.lastname: Thorndyke
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindahl
authors.forename: Dorothe
authors.initials: D
authors.lastname: Spillmann
mesh_terms: D000818:Animals; D016466:CHO Cells; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D003871:Dermatan Sulfate / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004357:Drug Synergism; D004447:Echinodermata / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006025:Glycosaminoglycans; D016222:Fibroblast Growth Factor 2; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates
keywords: brittlestar; chondroitin sulfate; dermatan sulfate; fibroblast growth factor 2