High plasma thiocyanate levels modulate protein damage induced by myeloperoxidase and perturb measurement of 3-chlorotyrosine

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• 作者：Jihan Talib^a ; David I. Pattison^a ; ^b ; Jason A. Harmer^a ; ^c ; David S. Celermajer^a ; ^c ; Michael J. Davies^a ; ^b ; ^{daviesm@hri.org.au}
• 关键词：BSA ; bovine serum albumin ; 3-ClTyr ; 3-chlorotyrosine ; di-Tyr ; 3 ; 3&prime ; -dityrosine ; LC&ndash ; MS ; liquid chromatography&ndash ; mass spectrometry ; MetS(O) ; methionine sulfoxide ; MetS(O)2 ; methionine sulfone ; MPO ; myeloperoxidase ; PBS ; phosphate-buffered sal
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：1 July, 2012
• 卷：53
• 期：1
• 页码：20-29
• 文件大小：819 K

摘要

Smokers have an elevated risk of atherosclerosis but the origin of this elevated risk is incompletely defined, though increasing evidence supports a role for the oxidant-generating enzyme myeloperoxidase (MPO). In previous studies we have demonstrated that smokers have elevated levels of thiocyanate ions (SCN^{鈭?/sup>), relative to nonsmokers, and increased thiol oxidation, as SCN鈭?/sup> is a favored substrate for MPO, and the resulting hypothiocyanous acid (HOSCN) targets thiol groups rapidly and selectively. In this study we show that increased HOSCN formation by MPO diminishes damage to nonthiol targets on both model proteins and human plasma proteins. Thus high SCN鈭?/sup> levels protect against HOCl- and MPO-mediated damage to methionine, tryptophan, lysine, histidine, and tyrosine residues on proteins. Furthermore, levels of the HOCl-mediated marker compound 3-chlorotyrosine and the cross-linked product dityrosine are decreased. Plasma protein 3-chlorotyrosine levels induced by HOCl exposure in nonsmokers are elevated over the levels detected in smokers when exposed to identical oxidative insult (P<0.05), and a strong inverse correlation exists between plasma SCN鈭?/sup> levels and 3-chlorotyrosine concentrations (r=0.6182; P<0.0001). These correlations were also significant for smokers (r=0.2724; P<0.05) and nonsmokers (r=0.4141; P<0.01) when analyzed as individual groups. These data indicate that plasma SCN鈭?/sup> levels are a key determinant of the extent and type of protein oxidation induced by MPO on isolated and plasma proteins and that smoking status and resulting high SCN鈭?/sup> levels can markedly modulate the levels of the widely used biomarker compound 3-chlorotyrosine.}