乙尼特通过独特的蛋白质醇反应机制诱导结构相关的细胞毒性
Kirsten Yeung1,2, Linna Xie1, Pranav Nair1
1Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
毒性饮用水副产品的酸二 (HANs) 呈现结构依赖的毒性. 它们的机制涉及与细胞醇的反应,与二乙尼特 (DBAN) 显示独特的基因介导通路.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 生物化学 生物化学
背景情况:
- 乙二 (HANs) 是饮用水中普遍存在的有毒消毒副产品.
- 目前尚不完全了解HANs毒性背后的精确机制.
- 调查结构-活动关系对于评估HAN的健康风险至关重要.
研究的目的:
- 阐明六个代表性的HANS的体外毒性机制.
- 为了将HANs的化学结构与其细胞毒性作用相关联.
- 识别有毒HANs的特定细胞点和反应途径.
主要方法:
- 利用了补充的生物分析方法,包括基于活动的蛋白质概况 (ABPP) 和枪支蛋白质组学.
- 采用谷氨 (GSH) 作为一种硫醇替代物来研究HANs的反应动力学.
- 应用电子磁共振 (EPR) 谱学来研究基质介导反应.
主要成果:
- 双甲 (DBAN) 呈现出显著的细胞毒性和氧化应激,与其他多化HANs (多HANs) 不同.
- 有毒的HANs与蛋白质二醇形成添加物,表明二醇反应性是关键的毒性机制.
- 单和多HAN与GSH表现出不同的反应途径,而DBAN则涉及激素中间体.
结论:
- HANs的毒性在结构上是有选择性的,由与细胞醇的明显反应驱动.
- 特定的抗氧化蛋白 (SOD1,CSTB,GAPDH) 是毒性HANs在氨酸残留物中的目标.
- 了解这些机制对于评估饮用水中HANs对健康的影响至关重要.
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