title: The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro.
abstract: The effect of reactive oxygen species (ROS) on the chemical structure of glycosaminoglycans (GAG) was studied in order to consider their role in connective tissue damage during an inflammatory disease state such as periodontal disease. GAG were exposed to a radical generating system for 1 h and analysed by gel filtration for fragmentation and chemically with respect to uronic acid, hexosamine and sulfate content. Non-sulfated GAG, hyaluronan and chondroitin, were most susceptible to depolymerisation and chemical modification of uronic acid and hexosamine residues by ROS. Depolymerisation and chemical modification of sulfated GAG, chondroitin 4-sulfate, dermatan sulfate and heparan sulfate was significantly less than for non-sulfated GAG. The highly sulfated GAG heparin showed minimal depolymerisation by ROS, but uronic acid residues were readily modified. Analysis of the ROS-exposed residues suggests that uronic acid is capable of degrading to a 3-carbon aldehyde, malondialdehyde. Chondroitin sulfate exposed to ROS resulted in marginal desulfation. The results suggest that the presence of sulfate on the GAG chain may protect the molecule against ROS attack. However, chemical modification of GAG may affect proteoglycan function and be of importance in considering connective tissue destruction in a variety of pathological situations, including periodontal disease.
authors.affiliation: Department of Basic Dental Science, Dental School, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: R
authors.initials: R
authors.lastname: Moseley
authors.forename: R
authors.initials: R
authors.lastname: Waddington
authors.forename: P
authors.initials: P
authors.lastname: Evans
authors.forename: B
authors.initials: B
authors.lastname: Halliwell
authors.forename: G
authors.initials: G
authors.lastname: Embery
mesh_terms: D002809:Chondroitin Sulfates / Q000737:chemistry; D002850:Chromatography, Gel; D003871:Dermatan Sulfate / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D006497:Heparan Sulfate / Q000737:chemistry; D006595:Hexosamines / Q000032:analysis; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013431:Sulfates / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry; D014574:Uronic Acids / Q000032:analysis
chemical_list: D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006595:Hexosamines; D017382:Reactive Oxygen Species; D013431:Sulfates; D017392:Thiobarbituric Acid Reactive Substances; D014574:Uronic Acids