THE CHEMICAL MODIFICATION OF GLYCOSAMINOGLYCAN STRUCTURE BY OXYGEN-DERIVED SPECIES IN-VITRO

The effect of reactive oxygen species (ROS) on the chemical structure of glycosaminoglycans (GAG) was studied in order to consider their rol e in connective tissue damage during an inflammatory disease state suc h as periodontal disease. GAG were exposed to a radical generating sys tem for 1 h and analysed by gel filtration for fragmentation and chemi cally with respect to uronic acid, hexosamine and sulfate content. Non -sulfated GAG, hyaluronan and chondroitin, were most susceptible to de polymerisation and chemical modification of uronic acid and hexosamine residues by ROS. Depolymerisation and chemical modification of sulfat ed GAG, chondroitin 4-sulfate, dermatan sulfate and heparan sulfate wa s significantly less than for non-sulfated GAG. The highly sulfated GA G heparin showed minimal depolymerisation by ROS, but uronic acid resi dues were readily modified. Analysis of the ROS-exposed residues sugge sts that uronic acid is capable of degrading to a 3-carbon aldehyde, m alondialdehyde. Chondroitin sulfate exposed to ROS resulted in margina l desulfation. The results suggest that the presence of sulfate on the GAG chain may protect the molecule against ROS attack. However, chemi cal modification of GAG may affect proteoglycan function and be of imp ortance in considering connective tissue destruction in a variety of p athological situations, including periodontal disease.