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Cited by 100Neutrophil, Myeloperoxidase and Oxidative MechanismsProteoglycans and glycosaminoglycans researchRedox biology and oxidative stress

Hypochlorite and superoxide radicals can act synergistically to induce fragmentation of hyaluronan and chondroitin sulphates

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REES, Martin D., HAWKINS, Clare L., DAVIES, Michael J.·2004·Biochemical Journal
DOI 10.1042/bj20040148PMC PMC1133775
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Abstract

Activated phagocytes release the haem enzyme MPO (myeloperoxidase) and also generate superoxide radicals (O2•−), and hence H2O2, via an oxidative burst. Reaction of MPO with H2O2 in the presence of chloride ions generates HOCl (the physiological mixture of hypochlorous acid and its anion present at pH 7.4). Exposure of glycosaminoglycans to a MPO–H2O2–Cl− system or reagent HOCl generates long-lived chloramides [R-NCl-C(O)-R′] derived from the glycosamine N-acetyl functions. Decomposition of these species by transition metal ions gives polymer-derived amidyl (nitrogen-centred) radicals [R-N•-C(O)-R′], polymer-derived carbon-centred radicals and site-specific strand scission. In the present study, we have shown that exposure of glycosaminoglycan chloramides to O2•− also promotes chloramide decomposition and glycosaminoglycan fragmentation. These processes are inhibited by superoxide dismutase, metal ion chelators and the metal ion-binding protein BSA, consistent with chloramide decomposition and polymer fragmentation occurring via O2•−-dependent one-electron reduction, possibly catalysed by trace metal ions. Polymer fragmentation induced by O2•− [generated by the superoxide thermal source 1, di-(4-carboxybenzyl)hyponitrite] was demonstrated to be entirely chloramide dependent as no fragmentation occurred with the native polymers or when the chloramides were quenched by prior treatment with methionine. EPR spin-trapping experiments using 5,5-dimethyl1-pyrroline-N-oxide and 2-methyl-2-nitrosopropane have provided evidence for both O2•− and polymer-derived carbon-centred radicals as intermediates. The results obtained are consistent with a mechanism involving one-electron reduction of the chloramides to yield polymer-derived amidyl radicals, which subsequently undergo intramolecular hydrogen atom abstraction reactions to give carbon-centred radicals. The latter undergo fragmentation reactions in a site-specific manner. This synergistic damage to glycosaminoglycans induced by HOCl and O2•− may be of significance at sites of inflammation where both oxidants are generated concurrently.

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  1. [11]Fosang A. J. Matrix proteoglycans. In: Comper W. D., editor. Extracellular Matrix: Molecular Components and Interactions. vol. 2. Harwood Academic, Amsterdam; 1996. pp. 200–229. [Google Scholar]
  2. [37]Bielski B. H. J., Cabelli D. E., Arudi R. L., Ross A. B. Reactivity of HO2/O2 − radicals in aqueous solution. J. Phys. Chem. Ref. Data. 1985;14:1041–1100. [Google Scholar]

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Authors
REES, M. D., HAWKINS, C. L., & DAVIES, M. J.
Affiliations
The Heart Research Institute (AU)
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2004-06-22
Volume
381
Issue
1
Pages
175-184
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj20040148
PMC
PMC1133775
OpenAlex
W2102357280
Cited by
100
References
72
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 10 · 2012: 7
FWCI
2.41
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
hypochlorous acid, superoxide, hyaluronic acid, chondroitin sulfate, myeloperoxidase, respiratory burst, one-electron reduction, amidyl radicals, carbon-centered radicals, hydrogen abstraction, superoxide dismutase, metal ion catalysis, inflammation, chain scission
MeSH terms
Carbohydrate Sequence, Chloramines, Chondroitin Sulfates, Drug Synergism, Electron Spin Resonance Spectroscopy, Glycosaminoglycans, Hyaluronic Acid, Hypochlorous Acid, Superoxides, Spin Trapping

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