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分子和计算研究揭示了Per-和多基基物质可以破坏蛋白质胺-DNA相互作用,可能诱导DNA损伤

Federica Musella¹, Maria Grazia Guarnieri¹, Simona Amore¹

¹Department of Biology, University of Naples Federico II, 80126 Naples, Italy.

|September 27, 2025

概括

环境污染物,如和多基物质 (PFAS),可以通过改变精子核基本蛋白 (SNBP) 和导致DNA损伤,损害男性生育能力. 这项研究表明,暴露于PFAS会导致SNBP的改变,减少DNA的保护,以及人类精子中的显著DNA碎片化.

科学领域:

环境科学环境科学
生殖生物学生殖生物学
毒理学毒理学毒理学

背景情况:

人类精子的染色质结构依赖于蛋白胺-DNA相互作用.
众所周知,环境污染物,如per-和多醇基物质 (PFAS),会对生殖健康产生不利影响.
以前的研究表明,在威尼托地区暴露于PFAS会改变精子核基本蛋白 (SNBP),降低精子抗氧化活性,增加脂氧化物.

研究的目的:

分析SNBP中的原氨酸与氨酸的比率.
量化SNBP诱导的DNA损伤,在血清 perfluorooctanoic 酸 (PFOA) 水平升高的个体中.
研究PFAS和人类原胺之间的分子相互作用,以了解DNA损伤的机制.

主要方法:

在高血清PFOA水平的受试者中分析SNBP和DNA损伤的横截面研究.
测量质氨酸与胰岛素的比率,并量化DNA损伤.
分子对接分析以模拟PFAS,DNA和原胺之间的相互作用.

主要成果:

所有血清PFOA超过值的个体都显示了三级DNA损伤.
在这些人中,SNBP表现出改变的原胺 - 希斯比率,通常转向原胺.
在亲氧化条件下,SNBPs显示DNA保护能力降低.
分子对接揭示了稳定的PFAS-DNA复合体,以及PFAS与蛋白胺上的DNA结合部位的潜在竞争.

结论:

暴露于PFAS可能会改变原氨基素比率,并降低SNBP的DNA保护能力.
通过与原胺和DNA相互作用,PFAS可能会诱导人类精子中的DNA损伤,可能形成三元 adduct.
这些发现表明,PFAS诱导的氧化应激会对男性生育能力产生不良影响.

关键词:

造成的DNA损伤是DNA损伤.在PFAS中,有很多方法.人类的精子,人类的精子.分子对接的分子对接.蛋白胺-DNA相互作用

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