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吸烟者和肺癌患者体内的硝化和氧化血浆蛋白。

Nitrated and oxidized plasma proteins in smokers and lung cancer patients.

作者信息

Pignatelli B, Li C Q, Boffetta P, Chen Q, Ahrens W, Nyberg F, Mukeria A, Bruske-Hohlfeld I, Fortes C, Constantinescu V, Ischiropoulos H, Ohshima H

机构信息

International Agency for Research on Cancer, Lyon, France.

出版信息

Cancer Res. 2001 Jan 15;61(2):778-84.

PMID:11212282
Abstract

Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western-blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins.

摘要

吸烟是肺癌和其他呼吸系统疾病的一个病因。香烟烟雾中存在的氧化剂和/或吸烟者肺内形成的氧化剂可能引发对DNA和细胞成分的氧化和硝化损伤,从而导致癌症发生。我们运用免疫斑点法和蛋白质印迹分析,对从52例肺癌患者和43名对照者(重度和轻度吸烟者、接触或未接触环境烟草烟雾的非吸烟者)采集的血浆样本中的硝化(含硝基酪氨酸)蛋白和氧化(含羰基)蛋白进行了检测。肺癌患者血浆中硝化蛋白的水平显著高于对照者(P = 0.003)。另一方面,吸烟者血浆中氧化蛋白的水平显著高于非吸烟者(P < 0.001)。蛋白质印迹分析显示存在两到五种硝化蛋白和一种氧化蛋白。我们使用针对人血浆蛋白的八种不同抗体进行免疫沉淀和蛋白质印迹分析,确定纤维蛋白原、转铁蛋白、纤溶酶原和铜蓝蛋白为硝化蛋白,纤维蛋白原是肺癌患者和吸烟者人血浆中唯一的氧化蛋白。我们的结果表明,吸烟会增加氧化应激,并且在肺癌发生过程中,活性氮物质的形成会导致血浆蛋白的硝化和氧化。

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