High plasma thiocyanate levels in smokers are a key determinant of thiol oxidation induced by myeloperoxidase

Research output: Contribution to journalJournal articleResearchpeer-review

Philip E Morgan, David I Pattison, Jihan Talib, Fiona A Summers, Jason A Harmer, David S Celermajer, Clare Louise Hawkins, Michael Jonathan Davies

Smokers have an elevated risk of atherosclerosis but the origins of this elevated risk are incompletely defined, though evidence supports an accumulation of the oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall. We hypothesized that smokers would have a high level of thiocyanate (SCN(-)), a preferred substrate for MPO, which in turn would predispose to thiol oxidation, an established independent risk factor for atherosclerosis. In this study it is shown that on exposure to MPO/H(2)O(2), thiols on plasma proteins from nonsmokers were increasingly oxidized with increasing added SCN(-) concentrations. Plasma from smokers contained significantly higher endogenous levels of SCN(-) than that from nonsmokers (131±31 vs 40±24 μM, P<0.0001). When plasma from smokers and nonsmokers was exposed to MPO/H(2)O(2)-stimulated oxidation, a strong positive correlation (r=0.8139, P<0.0001) between the extent of thiol oxidation and the plasma SCN(-) concentrations was observed. Computational calculations indicate a changeover from HOCl to HOSCN as the major MPO-generated oxidant in plasma, with increasing SCN(-) levels. These data indicate that plasma SCN(-) levels are a key determinant of the extent of thiol oxidation on plasma proteins induced by MPO, and implicate HOSCN as an important mediator of inflammation-induced oxidative damage to proteins in smokers.

Original languageEnglish
JournalFree Radical Biology & Medicine
Volume51
Issue number9
Pages (from-to)1815-22
Number of pages8
ISSN0891-5849
DOIs
Publication statusPublished - 1 Nov 2011
Externally publishedYes

    Research areas

  • Adult, Female, Humans, Male, Oxidation-Reduction, Peroxidase, Smoking, Sulfhydryl Compounds, Thiocyanates

ID: 129669499