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Glycosaminoglycans are fragmented by hydroxyl, carbonate, and nitrogen dioxide radicals in a site-selective manner: implications for peroxynitrite-mediated damage at sites of inflammation

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Glycosaminoglycans (long-chain polysaccharides) are major components of the extracellular matrix, glycocalyx, and synovial fluid. These materials provide strength and elasticity to tissues and play a key role in regulating cell behavior. Modifications to these materials have been linked to multiple human pathologies. Although modification may occur via both enzymatic and nonenzymatic mechanisms, there is considerable evidence for oxidant-mediated matrix damage. Peroxynitrite (ONOO(-)/ONOOH) is a potential mediator of such damage, as elevated levels of this oxidant are likely to be present at sites of inflammation. In this study we demonstrate that hyaluronan and chondroitin sulfate are extensively depolymerized by HO(.) and CO3(.-), but not NO2(.), which may be formed from peroxynitrite. Polymer fragmentation is shown to be dependent on the radical flux, to be O2-independent, and to occur in a site-selective manner as indicated by the detection of disaccharide fragments. EPR spin trapping experiments with polymers, oligomers, and component monosaccharides, including 13C-labeled materials, have provided evidence for the formation of specific carbon-centered sugar-derived radicals. The time course of formation of these radicals is consistent with these species being involved in polymer fragmentation.

OriginalsprogEngelsk
TidsskriftFree Radical Biology & Medicine
Vol/bind47
Udgave nummer4
Sider (fra-til)389-400
Antal sider12
ISSN0891-5849
DOI
StatusUdgivet - 15 aug. 2009
Eksternt udgivetJa

ID: 129670395