S-Nitrosoglutathione Reductase An Important Regulator in Human Asthma
S-Nitrosoglutathione Reductase An Important Regulator in Human Asthma
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DOI：
10.1164/rccm.200901-0158oc
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发表时间：
2009-08-01
影响因子：
24.7
通讯作者：
Kraft, Monica
中科院分区：
文献类型：
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作者：
Que, Loretta G.;Yang, Zhonghui;Kraft, Monica
原理：通过S-亚硝基硫醇（SNO）形成介导的一氧化氮生物活性对支气管张力有显著影响。S-亚硝基谷胱甘肽是一种内源性支气管扩张剂，在哮喘呼吸衰竭儿童和接受节段性气道激发的哮喘成人中减少。最近，我们发现S-亚硝基谷胱甘肽还原酶（GSNOR）调节内源性SNO。GSNOR基因缺失的小鼠在过敏性asthma model.Objectives中免受气道高反应性的影响：我们假设GSNOR在人类哮喘中增加，并与肺SNO含量和气道反应性相关。研究方法：我们招募了36名轻度哮喘受试者，FEV 1为88.5 +/- 2.3%预测值，34名健康对照受试者，FEV 1为100.7 +/- 2.5%预测值。所有受试者均行支气管肺泡灌洗（BAL）。细胞计数，分化，GSNOR活性，和SNO水平测定BAL.Measurements和主要结果：与对照BAL相比，哮喘BAL中SNO含量降低，并与BAL细胞裂解物中GSNOR表达呈负相关。哮喘患者BALF中GSNOR活性显著高于对照组，且与引起FEV 1下降20%的乙酰甲胆碱激发浓度呈负相关。结论：GSNOR是哮喘患者气道SNO含量和气道高反应性的重要调节因子。
Rationale: Nitric oxide bioactivity, mediated through the formation of S-nitrosothiols (SNOs), has a significant effect on bronchomotor tone. S-Nitrosoglutathione is an endogenous bronchodilator that is decreased in children with asthmatic respiratory failure and in adults with asthma undergoing segmental airway challenge. Recently we showed that S-nitrosoglutathione reductase (GSNOR) regulates endogenous SNOs. Mice with genetic deletion of GSNOR are protected from airway hyperresponsivity in an allergic asthma model.Objectives: We hypothesized that GSNOR is increased in human asthma and correlates with lung SNO content and airway reactivity. Methods: We recruited 36 subjects with mild asthma with FEV1 88.5 +/- 2.3% predicted and 34 healthy control subjects with FEV1 100.7 +/- 2.5% predicted. Bronchoalveolar lavage (BAL) was performed in all subjects. Cell counts, differentials, GSNOR activity, and SNO levels were determined in BAL.Measurements and Main Results: SNO content was decreased in asthmatic BAL compared with control BAL and correlated inversely with GSNOR expression in BAL cell lysates. Furthermore, GSNOR activity measured from BAL samples was significantly increased in subjects with asthma compared with control subjects and correlated inversely with the provocative concentration of methacholine causing a 20% decrease in FEV1.Conclusions: These findings suggest that GSNOR is an important regulator of airway SNO content and airways hyperresponsiveness in human asthma.