长期暴露于会抑制蛋白质体和自体蛋白质降解
Isabell I Augenstein1, Alexandra N Nail2, Ana P Ferragut Cardoso2
1Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
Environmental toxicology and pharmacology
|February 25, 2024
概括
长期暴露在无机 (iAs) 中会破坏细胞蛋白质降解途径. 这项研究揭示了iAs抑制了全方位蛋白质体系统 (UPS) 并抑制了自,影响了与癌症相关的细胞功能.
科学领域:
- 分子生物学分子生物学
- 环境毒理学环境毒理学
- 癌症研究 癌症研究
背景情况:
- 乌比基保护体系统 (UPS) 的失调和自与癌症的发展有关.
- 指蛋白调节这些关键的细胞通路.
- 三价无机 (iAs) 可以取代,干扰指蛋白的功能.
研究的目的:
- 调查长期暴露于100 nM iAs的环境对UPS的影响.
- 测试iAs暴露抑制UPS并激活自作为补偿反应的假设.
- 阐明IA对自开始和蛋白质降解的影响.
主要方法:
- 暴露人体皮肤 (HaCaT,Ker-CT) 和肺 (BEAS-2B) 细胞系0或100nM iAs7-8周.
- 通过XBP1拼接 (RT-PCR) 来量化内质网膜 (ER) 应激.
- 评估蛋白质体降解和自开始/完成使用免疫血栓.
主要成果:
- 长期的IA暴露显著抑制了皮肤和肺细胞系中的UPS.
- iAs启动了自,但同时抑制了自蛋白质降解.
- 评估ER压力标志物,表明细胞应激反应.
结论:
- 长期环境iAs暴露会抑制关键蛋白质降解途径,包括UPS和自.
- 数据表明一个复杂的相互作用,其中IA最初激活自但最终损害其降解功能.
- 由IA破坏细胞平衡的这种破坏可能会导致癌症的开始和进展.
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