4-hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease
4-hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease
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DOI：
10.1164/rccm.2110101
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发表时间：
2002-08-15
影响因子：
24.7
通讯作者：
De Boer, WI
中科院分区：
文献类型：
--
作者：
Rahman, I;van Schadewijk, AAM;De Boer, WI
吸烟导致肺中的氧化应激和炎症，其参与慢性阻塞性肺疾病（COPD）的发病机制。4-羟基-2-壬烯醛（4-HINE）是一种高活性的脂质过氧化扩散产物，是氧化剂诱导的细胞信号传导和凋亡的关键介质。4-HNE对半胱氨酸、组氨酸和赖氨酸基团具有高亲和力，并形成直接的蛋白质加合物。我们研究了从患有和不患有COPD的受试者获得的肺组织中4-HNE修饰的蛋白质的存在。我们研究了23名有相似吸烟史的吸烟者，包括COPD患者（n = 11; FEV 1 < 70%预测值）或非COPD患者（n = 12; FEV 1> 84%预测值），均接受了肺切除术。由于4-HNE和转化生长因子-β（TGF-β（1））可调节肺细胞中γ-谷氨酰半胱氨酸合成酶（γ-GCS）mRNA水平，因此我们评估了4-HNE修饰的蛋白水平、FEV 1、γ-GCS和TGF-β（1）之间的关系。与非COPD受试者相比，COPD受试者气道和肺泡上皮细胞、内皮细胞和中性粒细胞中4-HNE修饰的蛋白水平升高（p < 0.01）。我们还观察到肺泡上皮细胞、气道内皮细胞和中性粒细胞中4-HNE加合物水平与FEV 1呈显著负相关（p < 0.05），而气道和肺泡上皮细胞中4-HNE加合物与TGF-β 1蛋白和mRNA以及γ-GCS mRNA水平呈正相关（p < 0.01）。4-HNE水平升高可能参与了COPD患者肺部炎症的信号转导过程，导致促炎介质和抗氧化保护基因表达失衡。
Cigarette smoking results in oxidative stress and inflammation in the lungs, which are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). 4-Hydroxy-2-nonenal (4-HINE), a highly reactive diffusible product of lipid peroxidation, is a key mediator of oxidant-induced cell signaling and apoptosis. 4-HNE has a high affinity toward cysteine, histidine, and lysine groups and forms direct protein adducts. We investigated the presence of 4-HNE-modified proteins in lung tissue obtained from subjects with and without COPD. We studied 23 current or ex-smokers with similar smoking histories with COPD (n = 11; FEV1 < 70% predicted) or without COPD (n = 12; FEV1 > 84% predicted) who had undergone lung resection. As 4-HNE and transforming growth factor-P, (TGF-beta(1)) can modulate gamma-glutamylcysteine synthetase (gamma-GCS) mRNA levels in lung cells, we assessed the relations between 4-HNE-modified protein levels, FEV1, gamma-GCS, and TGF-beta(1). 4-HNE-modified protein levels were elevated in airway and alveolar epithelial cells, endothelial cells, and neutrophils in subjects with COPD, compared with the levels in subjects without COPD (p < 0.01). We also observed a significant inverse correlation between the levels of 4-HNE adducts in alveolar epithelium, airway endothelium, and neutrophils and FEV1 (p < 0.05) and a positive correlation between 4-HNE adducts and TGF-beta(1) protein and mRNA as well as gamma-GCS mRNA levels in airway and alveolar epithelium (p < 0.01). The elevated levels of 4-HNE may play a role in the signaling events in lung inflammation leading to the imbalance of the expression of both proinflammatory mediators and protective antioxidant genes in COPD.