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接触柴油机废气与人类血清白蛋白的 Cys34/Lys525 加合物组改变。

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

School of Public Health, University of California, Berkeley, CA, USA.

出版信息

Environ Toxicol Pharmacol. 2022 Oct;95:103966. doi: 10.1016/j.etap.2022.103966. Epub 2022 Sep 5.

Abstract

We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.

摘要

我们研究了接触致癌柴油发动机废气 (DEE) 是否与人体血清白蛋白 (HSA) 残基中加合物水平的改变有关。使用纳升液相色谱-高分辨质谱 (nLC-HRMS) 测量了 54 名柴油发动机厂工人和 55 名未暴露对照者血浆样本中 Cys34 和 Lys525 残基的加合物。使用靶向性的加合物组学和生物信息学管道来寻找 Cys34/Lys525 加合物组修饰的特征。为了确定 DEE 暴露和未暴露参与者之间加合物的改变,我们使用了一种集成特征选择方法,该方法对线性回归和惩罚逻辑回归的发现进行排名和组合,然后将重要发现与随机森林确定的发现进行汇总。我们检测到 40 个 Cys34 和 9 个 Lys525 加合物。在这些发现中,我们有证据表明,6 个 Cys34 加合物在 DEE 暴露和未暴露参与者之间发生了改变(即 841.75、851.76、856.10、860.77、870.43 和 913.45)。这些加合物与抗氧化活性有关。

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Chem Res Toxicol. 2021 Dec 20;34(12):2549-2557. doi: 10.1021/acs.chemrestox.1c00311. Epub 2021 Nov 17.

本文引用的文献

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Extending the HSA-Cys34-Adductomics Pipeline to Modifications at Lys525.将 HSA-Cys34 加合物组学方法扩展到赖氨酸 525 的修饰。
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