细胞内膜网膜应激和自与三乙诱导的肝毒性有关
Weiqi Liang1, Lingling Fu1, Mei Feng1
1School of Public Health, Health Science Center, Ningbo University, Ningbo 315211, China.
Toxics
|July 28, 2023
概括
三乙烯 (TBT) 通过首先诱导内分泌网膜应激和自,然后是亡来引起肝损伤. 这项研究揭示了TBT肝毒性在人类肝细胞中的新机制.
科学领域:
- 环境毒理学环境毒理学
- 细胞生物学 细胞生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 三乙 (TBT) 是一种广泛存在的水生污染物,因其严重的毒性而闻名,特别是对肝脏.
- 以前的研究表明,TBT诱导的肝毒性涉及亡,但之前的分子事件仍然不清楚.
研究的目的:
- 用蛋白质组分析研究人类肝细胞 (HL7702) 中的TBT诱导肝毒性早期分子机制.
- 阐明细胞事件的序列,包括内质网膜应激和自,先于亡.
主要方法:
- 用不同度的TBT (2μM和4μM) 治疗的HL7702细胞的蛋白质组分析.
- 传输电子显微镜用于观察细胞超结构.
- 对内质网膜应激 (PERK,ATF6,BiP,CHOP) 和自 (Beclin1,Atg蛋白,LC3) 的关键蛋白标记物的分析.
- 检测XBP1mRNA拼接的情况.
主要成果:
- 低剂量TBT (2μM) 诱导了未折叠的蛋白质反应和内质网膜应激,由升高的PERK,ATF6,BiP,CHOP和XBP1拼接证明.
- 较高的TBT剂量 (4μM) 激活了自,由增加的Beclin1,Atg蛋白和LC3-II转化表明.
- 在较高度下,TBT诱导的损伤压倒了自,导致了亡.
结论:
- 结核酸诱导的肝毒性通过一系列的细胞内网膜应激,自激活和最终的亡而进展.
- 这项研究确定了涉及TBT对肝细胞毒性影响的新型分子通路.
- 这些发现为环境污染物引起的肝损伤的机制提供了关键的见解.
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