S100A8 and S100A9-oxidant scavengers in inflammation
S100A8 and S100A9-oxidant scavengers in inflammation
复制标题
DOI：
10.1016/j.freeradbiomed.2012.12.012
复制
发表时间：
2013-05-01
影响因子：
7.4
通讯作者：
Geczy, Carolyn L.
中科院分区：
文献类型：
--
作者：
Gomes, Lincoln H.;Raftery, Mark J.;Geczy, Carolyn L.
S100 A8和S100 A9通常被认为是促炎性的。活化的吞噬细胞产生的次卤酸促进小鼠S100 A8的新修饰，但对人S100 A8的修饰是不确定的，没有证据表明这些蛋白质在人类疾病中抑制氧化剂。重组S100 A8对等摩尔比的HOCl非常敏感，HOCl在单个Cys（42）残基上产生亚磺酸和磺酸中间体和新的氧杂噻唑烷氧化物/二氧化物形式（质量加成，m/z +30和+46）。还存在Met（78）（O）和Trp（64）（+16）。HOBr生成磺酸中间体并氧化Trp（54）（+16）。recS 100 A9 HOCl中单个Cys（3）残基氧化的证据较弱; Met（63）、Met（81）、Met（83）和Met（94）在体外转化为Met（O）。与对照组相比，氧化S100 A8在哮喘患者的肺中显著，并且在痰中显著升高，而S100 A8和S100 A9没有显著增加。氧化单体S100 A8是哮喘痰液中的主要成分，其修饰（包括氧噻唑烷加合物）与体外HOCl产生的修饰相似。氧化Met（63）、Met（81）和Met（94）在哮喘痰液中的S100 A9中存在不同程度的氧化Met。结果具有广泛的影响条件下，次卤酸氧化剂产生的活化吞噬细胞。在人类疾病中鉴定的新型S100 A8 Cys衍生物是体外产生的那些衍生物的典型，这强烈支持S100 A8有助于氧化应激期间的抗氧化防御的概念。皇冠版权所有（C）2013由Elsevier Inc.发布。All rights reserved.
S100A8 and S100A9 are generally considered proinflammatory. Hypohalous acids generated by activated phagocytes promote novel modifications in murine S100A8 but modifications to human S100A8 are undefined and there is no evidence that these proteins scavenge oxidants in human disease. Recombinant S100A8 was exquisitely sensitive to equimolar ratios of HOCl, which generated sulfinic and sulfonic acid intermediates and novel oxathiazolidine oxide/dioxide forms (mass additions, m/z +30 and +46) on the single Cys(42) residue. Met(78)(O) and Trp(64)(+16) were also present. HOBr generated sulfonic acid intermediates and oxidized Trp(54)(+16). Evidence for oxidation of the single Cys(3) residue in recS100A9 HOCl was weak; Met(63), Met(81), Met(83), and Met(94) were converted to Met(O) in vitro. Oxidized S100A8 was prominent in lungs from patients with asthma and significantly elevated in sputum compared to controls, whereas S100A8 and S100A9 were not significantly increased. Oxidized monomeric S100A8 was the major component in asthmatic sputum, and modifications, including the oxathiazolidine adducts, were similar to those generated by HOCl in vitro. Oxidized Met(63), Met(81), and Met(94) were variously present in S100A9 from asthmatic sputum. Results have broad implications for conditions under which hypohalous acid oxidants are generated by activated phagocytes. Identification in human disease of the novel S100A8 Cys derivatives typical of those generated in vitro strongly supports the notion that S100A8 contributes to antioxidant defense during oxidative stress. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.