佐特醇紫外线稳定剂破坏了人体细胞中的表皮生长因子受体信号传递
Natalie C Sondermann1, Afaque A Momin2, Stefan T Arold2
1IUF - Leibniz-Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
Environment international
|July 18, 2024
概括
松紫外线稳定剂 (BUV) 污染了环境和人体. 这项研究揭示了BUVs与表皮生长因子受体 (EGFR) 结合,破坏其功能和细胞过程.
科学领域:
- 环境化学环境化学
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 类二紫外线稳定剂 (BUVs) 是一种持久且生物累积的环境污染物.
- 已在野生动物和人类中检测到BUV,引发了人们对其健康影响的担忧.
- 欧洲化学品署将一些BUV确定为非常令人担忧的物质.
研究的目的:
- 研究BUVs对人类表皮生长因子受体 (EGFR) 的机械效应.
- 确定EGFR作为BUVs的潜在细胞点.
- 为改善危险评估和潜在的治疗策略提供数据.
主要方法:
- 在Silico分子对接模拟中.
- 对EGFR的突变分析.
- 受体结合和内化试验.
- 对人类角质细胞下游信号事件 (ERK1/2酸化) 和细胞过程 (DNA合成) 的分析.
主要成果:
- BUVs,特别是化变体,与EGFR的细胞外域结合.
- 结合BUV可以抑制生长因子与EGFR的相互作用.
- BUVs抑制EGFR下游信号传递,包括ERK1/2酸化和人类角质细胞中的DNA合成.
结论:
- EGFR作为BUVs的血膜受体起作用.
- 这种相互作用为BUVs的生物效应提供了一个新的机制.
- 这些发现有助于对BUV的危险性评估,并可能为开发新的EGFR向药物提供信息.
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