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中国宣威和富源固体燃料使用者血清白蛋白Cys34加合物组分析

Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China.

作者信息

Lu Sixin S, Grigoryan Hasmik, Edmands William M B, Hu Wei, Iavarone Anthony T, Hubbard Alan, Rothman Nathaniel, Vermeulen Roel, Lan Qing, Rappaport Stephen M

机构信息

Department of Nutritional Sciences and Toxicology, College of Natural Resources, University of California , Berkeley, California 94720, United States.

Division of Environmental Health Sciences, School of Public Health, University of California , Berkeley, California 94720, United States.

出版信息

Environ Sci Technol. 2017 Jan 3;51(1):46-57. doi: 10.1021/acs.est.6b03955. Epub 2016 Dec 12.

Abstract

Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryptic peptides of HSA, containing Cys34 and prominent post-translational modifications. Putative adducts included Cys34 oxidation products, mixed disulfides, rearrangements, and truncations. The most significant differences in adduct levels across fuel types were observed for S-glutathione (S-GSH) and S-γ-glutamylcysteine (S-γ-GluCys), both of which were present at lower levels in subjects exposed to combustion products than in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene, the largest reductions in levels of S-GSH and S-γ-GluCys relative to controls were observed for users of smoky coal, compared to users of smokeless coal and wood. These results point to possible depletion of GSH, an essential antioxidant, and its precursor γ-GluCys in nonsmoking females exposed to indoor-combustion products in Xuanwei and Fuyuan, China.

摘要

中国宣威县和富源县因使用有烟煤烹饪和取暖造成室内空气污染,肺癌发病率位居世界之首。为了发现室内燃烧产物的潜在生物标志物,我们对29名使用有烟煤、无烟煤或木材的宣威和富源非吸烟女性以及10名使用电力或气体燃料的当地对照者的人血清白蛋白(HSA)Cys34位点的加合物进行了分析。我们的非靶向“加合物组学”方法检测到了50条HSA的胰蛋白酶肽段,其中包含Cys34以及显著的翻译后修饰。推定的加合物包括Cys34氧化产物、混合二硫键、重排和截短。在不同燃料类型中,S-谷胱甘肽(S-GSH)和S-γ-谷氨酰半胱氨酸(S-γ-GluCys)的加合物水平差异最为显著,这两种加合物在接触燃烧产物的受试者中的含量均低于对照组。在对年龄和空气中苯并(a)芘的个人测量值进行调整后,与使用无烟煤和木材的使用者相比,使用有烟煤的使用者的S-GSH和S-γ-GluCys水平相对于对照组下降幅度最大。这些结果表明,在中国宣威和富源接触室内燃烧产物的非吸烟女性中,必需抗氧化剂谷胱甘肽及其前体γ-GluCys可能会被消耗。

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