Production of reactive persulfide species in chronic obstructive pulmonary disease
Production of reactive persulfide species in chronic obstructive pulmonary disease
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慢性阻塞性肺疾病中活性过硫化物的生成
DOI：
10.1136/thoraxjnl-2016-209359
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发表时间：
2017-12-01
期刊：
影响因子：
10
通讯作者：
Ichinose, Masakazu
中科院分区：
文献类型：
--
作者：
Numakura, Tadahisa;Sugiura, Hisatoshi;Ichinose, Masakazu
背景氧化应激是慢性阻塞性肺疾病（COPD）的主要病因。最近被认为是有效的抗氧化剂，活性过硫化物和多硫化物物种是由胱硫醚β-合酶和胱硫醚γ-裂解酶生物合成的。COPD患者肺组织中活性过硫化物和多硫化物的产生尚不清楚。目的本研究的目的是检测轻中度COPD患者肺上皮细胞和上皮细胞衬里液（ELF）中活性过硫化物和多硫化物的产生，如谷胱甘肽过硫化物（GSSH）、半胱氨酸过硫化物（CysSSH）和谷胱甘肽三硫化物（GSSSH）。获得原代肺细胞、ELF和痰。细胞和ELF中反应性过硫化物和多硫化物的量通过液相色谱-串联质谱法测量，用β-（4-羟基苯基）乙基碘乙酰胺作为过硫化物/多硫化物的捕获剂。结果COPD患者肺细胞和ELF中GSSH、CysSSH和GSSSH的含量均降低，而ELF中GSSH、CysSSH和GSSSH的含量均降低。肺细胞中活性过硫化物和多硫化物含量与气流受限程度呈正相关。与此相反，在COPD患者的肺组织和痰细胞中的过氧化物酶的量增加。结论我们已经确定了减少反应性过硫化物和多硫化物物种在COPD患者的肺。这些数据表明，新检测到的抗氧化剂反应性过硫化物和多硫化物可能与COPD患者肺部的氧化还原平衡有关。
Background Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine beta-synthase and cystathionine gamma-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.Objectives The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lungresident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD.Methods Lung tissues, primary lung cells, ELF and sputum were obtained. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography-tandem mass spectrometry with beta-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/ polysulfides. The amounts of synthases in the lung tissues, sputum and primary cells were quantified.Results The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD.Conclusions We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.