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网络药理学和转录学揭示了雄激素受体作为6PPD-氨酸的潜在蛋白质标

Xiao-Liang Liao¹, Jia-Ming Zhou¹, Yujie Wang¹

¹Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China.

The Science of the total environment

|November 24, 2024

概括

N-(1,3-dimethylbutyl) -N'-phenyl-p-phenylenediamine quinone (6PPD-quinone,或6PPD-Q) 是一个新出现的环境污染物. 这项研究发现6PPD-Q作为雄激素受体激动剂,可能增加前列腺癌风险.

科学领域:

环境科学环境科学
毒理学毒理学毒理学
分子生物学分子生物学

背景情况:

N-(1,3-二甲基) -N' --p-phenylenediamine (6PPD-或6PPD-Q) 是大气颗粒中发现的一种新兴环境污染物,表明人类暴露的程度很高.
与6PPD-Q暴露相关的健康危害,特别是它对人类健康的影响,仍然在很大程度上是未知的.

研究的目的:

使用in silico方法识别6PPD-Q的潜在人体蛋白标.
研究6PPD-Q对人类健康的体外和体内影响,重点研究前列腺癌发生.
确定6PPD-Q是否表现出雄激素受体 (AR) 激动性及其对前列腺癌风险的影响.

主要方法:

基于受体的反向查和网络药理学被用来确定6PPD-Q的关键蛋白标.
一个支持矢量机器 (SVM) 模型被开发来预测AR激应/不活动.
为了验证,在实验室中进行了细胞增殖试验和小鼠前列腺组织的体内转录组分析.

主要成果:

确定了与前列腺癌发生相关的6PPD-Q的四个枢纽标,与雄激素受体 (AR) 具有强烈的结合亲和力.
通过SVM预测和基于细胞的测试,证实6PPD-Q表现出AR激动性.
暴露于6PPD-Q上调调节的Ar mRNA表达和相关的前列腺癌途径的环境现实的度.

结论:

6PPD-Q作为AR激动剂,导致下游基因交换活化.
这些发现表明,6PPD-Q可能在促进前列腺癌发生方面发挥作用,这表明对人类健康的潜在风险.

关键词:

6PPD - 氨酸 - 氨酸的使用情况雄激素受体的受体雄激素受体细胞增殖测定试验分子动力学模拟模型网络药理学网络药理学文字转录学 (Transcriptomics) 是一个学科.

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