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细胞内硫化会通过eIF2α酸化诱导压力颗粒的形成和转化抑制
S Kanno1, S Hirano2, J Monma-Otaki3
1Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. sanae@med.nagoya-cu.ac.jp.
Archives of toxicology
|April 9, 2025
概括
高度的硫化 (H2S) 会触发肺细胞中压力颗粒的形成,这是一种涉及eIF2α酸化的保护性反应. 这一过程限制了蛋白质合成,以减轻H2S诱导的细胞损伤.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 硫化 (H2S) 是一种有毒气体,会导致严重的呼吸损伤.
- 压力颗粒 (SG) 是细胞结构,在压力下形成以保护细胞.
- 了解H2S毒性机制对于呼吸系统健康至关重要.
研究的目的:
- 为了研究应力颗粒 (SG) 形成,以应对高H2S度.
- 阐明涉及H2S诱导的SG形成的分子途径.
- 确定特定细胞组件在H2S毒性的作用.
主要方法:
- 人类支气管BEAS-2B和CHO细胞暴露于不同度的NaHS (H2S来源).
- 对SG形成和细胞内H2S水平进行微观分析.
- 药物抑制/增强关键信号通路 (PERK,eIF2α,GSH,Trx) 的作用.
主要成果:
- 在暴露于NaHS后,细胞内H2S水平因剂量而异地增加.
- 在1小时内,单独的SG组件在两个细胞系中迅速形成.
- SG形成是由GSH,Trx,PERK的抑制剂/增强剂和综合应激反应调节的.
- eIF2α酸化显著增加,与SG形成和蛋白质合成减少相关.
结论:
- 在肺细胞中,H2S暴露会通过eIF2α酸化诱导SG形成和转化抑制.
- 谷氨 (GSH) 和硫素 (Trx) 似乎在缓解H2S诱导的SG形成中起着保护作用.
- PERK途径部分参与H2S诱导的SG形成,有助于保护细胞免受H2S毒性影响.
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