二烯及其衍生物通过激活基碳化合物受体转录激活增加肺部不良影响
Mei Wang1, Na Luo1, Yanpeng Gao1
1Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution control, Guangdong University of Technology, Guangzhou 510006, China; Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of Education, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China.
多环芳 (PAH) 衍生品比原始PAH具有更高的肺部健康风险. 这些化合物激活基碳化合物受体 (AhR),增加对人类肺部的不良影响.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 多环芳 (PAH) 及其衍生物是已知健康风险的环境污染物.
- 通过PAH衍生物影响人类健康,特别是肺部健康的具体机制,仍然在很大程度上未被探索.
研究的目的:
- 研究烯及其衍生物 (1-基烯,1-基烯,1-甲基烯) 对人类肺部健康的不良影响和作用机制.
- 阐明基碳化合物受体 (AhR) 激活在这些化合物的毒性中的作用.
主要方法:
- 实验室和体内实验模型被用于评估肺部健康影响.
- 用分子动力学模拟来确定与AhR的结合能量和相互作用.
- 对下游目标基因表达 (CYP1A1,CYP1B1) 和在AhR中的关键氨基酸相互作用的分析.
主要成果:
- 与pyrene相比,pyrene衍生物显示出更大的肺部健康风险.
- 观察到AhR的激活,导致CYP1A1和CYP1B1.1的表达变化.
- 分子动力学模拟表明,烯及其衍生物作为AhR激动剂,其中1-烯显示最强的结合和AhR激活.
- 在AhR中特定的氨基酸残留被确定为对差异性结合亲和力的关键.
结论:
- 通过AhR激活,PAH衍生物对人类肺部健康构成重大威胁.
- 该研究为了解PAH衍生物的毒理机制提供了一个框架.
- 由于PAH衍生物具有强大的生物活性,因此需要认真考虑PAH衍生物的不良影响.
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