S-Glutathionylated Serine Proteinase Inhibitors as Biomarkers for Radiation Exposure in Prostate Cancer Patients.
S-Glutathionylated Serine Proteinase Inhibitors as Biomarkers for Radiation Exposure in Prostate Cancer Patients.
复制标题
S-谷胱甘肽化丝氨酸蛋白酶抑制剂作为前列腺癌患者辐射暴露的生物标志物。
DOI：
10.1038/s41598-019-50288-9
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发表时间：
2019
影响因子：
4.6
通讯作者：
Tew,KennethD
中科院分区：
文献类型：
--
作者：
Zhang,Leilei;Zhang,Jie;Ye,Zhiwei;Manevich,Yefim;Townsend,DanyelleM;Marshall,DavidT;Tew,KennethD
在生物组织中，辐射引起活性氧（ROS）的形成，其中一些导致某些蛋白质半胱氨酸残基的连续氧化。由此产生的半胱氨酸自由基可通过s -谷胱甘肽化进行翻译后修饰。目前的临床试验旨在确定血液中的s -谷胱甘肽化丝氨酸蛋白酶抑制剂（蛇肽）是否可以用作辐射暴露的生物标志物。试验纳入56例接受放疗的男性前列腺癌患者，采用免疫印迹法评估s -谷胱甘肽化蛇肽A1和A3的水平。患者分为三组：(1)外束放射治疗（EBRT）；(2)近距离治疗（BT）；(3) EBRT和BT治疗前，各组未修饰和s -谷胱甘肽化蛇肽的基线血浆水平相似。我们发现放疗后患者血液中s -谷胱甘肽化蛇氨酸A1单体、三聚体和蛇氨酸A3单体的血浆水平升高。这些s -谷胱甘肽化蛇形蛋白水平的最大增加与放疗时间的延长相关。我们的结论是，定量患者血浆s -谷胱甘肽化蛇形蛋白是可行的，这些翻译后修饰的蛋白是测量辐射暴露的候选生物标志物。这为在一系列药物（如辐射）中使用这些生物标志物提供了一个平台，这些药物会产生活性氧。
In biological tissues, radiation causes the formation of reactive oxygen species (ROS), some of which lead to sequential oxidation of certain protein cysteine residues. Resultant cysteinyl radicals are subject to post-translational modification through S-glutathionylation. The present clinical trial was designed to determine if S-glutathionylated serine protease inhibitors (serpins) in blood could be used as biomarkers of exposure to radiation. 56 male prostate cancer patients treated with radiotherapy were enrolled in the trial and levels of S-glutathionylated serpins A1 and A3 were assessed by immunoblotting. Patients were classified into three groups: (1) external beam radiation therapy (EBRT); (2) brachytherapy (BT); (3) both EBRT and BT. Prior to treatment, baseline plasma levels of both unmodified and S-glutathionylated serpins were similar in each group. We identified elevated plasma levels of S-glutathionylated serpin A1 monomer, trimer and serpin A3 monomer in patient blood following radiation. Maximal increased levels of these S-glutathionylated serpins were correlated with increased duration of radiotherapy treatments. We conclude that it is practical to quantify patient plasma S-glutathionylated serpins and that these post-translationally modified proteins are candidate biomarkers for measuring radiation exposure. This provides a platform for use of such biomarkers in trials with the range of drugs that, like radiation, produce ROS.