title: High plasma thiocyanate levels in smokers are a key determinant of thiol oxidation induced by myeloperoxidase.
abstract: 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.
authors: The Heart Research Institute, Newtown, Sydney, NSW 2042, Australia.
authors: Philip E
authors: PE
authors: Morgan
authors: David I
authors: DI
authors: Pattison
authors: Jihan
authors: J
authors: Talib
authors: Fiona A
authors: FA
authors: Summers
authors: Jason A
authors: JA
authors: Harmer
authors: David S
authors: DS
authors: Celermajer
authors: Clare L
authors: CL
authors: Hawkins
authors: Michael J
authors: MJ
authors: Davies
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D012907:Smoking / Q000097:blood*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013861:Thiocyanates / Q000097:blood*
chemical_list: D013438:Sulfhydryl Compounds; D013861:Thiocyanates; D009195:Peroxidase; C031760:thiocyanate