酸通过ATF4/CTH/SQOR轴诱导细胞铁亡
Wupei Pan1, Xiaoyi Zou1, Wenxin Tang1
1School of Basic Medical Sciences, Yichun University, 576 XueFu Road, Yuanzhou District, Yichun 336000, PR China.
Biochemical pharmacology
|February 27, 2026
概括
酸通过破坏ATF4/CTH/SQOR通路,降低硫化和CoQ10H2水平,并损害抗氧化剂防御,导致损伤. 针对这一轴提供了一种新的治疗策略,用于预防ferroptosis诱导的毒性.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 酸 (SA) 与严重的损伤有关.
- SA诱导细胞铁亡,这是细胞死亡途径,GPX4或FSP1部分减轻.
- 在SA诱导的毒性背后的精确机制仍然不完全理解.
研究的目的:
- 为了阐明SA诱导的损伤的分子机制.
- 调查硫化 (H2S) 和辅酶Q10 (CoQ10H2) 在SA毒性的作用.
- 为了确定SA诱导的毒性新疗法目标.
主要方法:
- 细胞测定测量H2S,CoQ10H2,脂质过氧化和铁亡标志物.
- 对ATF4,CTH和SQOR的基因表达分析.
- 关键路径组件 (ATF4,CTH,SQOR,AOX) 的过度表达和沉默.
- 在体内研究使用SA处理的细胞和相关的基因操纵.
主要成果:
- 通过抑制ATF4,CTH和SQOR表达,SA降低了细胞H2S和CoQ10H2水平.
- SA诱导的铁亡与抗氧化剂防御和脂质过氧化受损有关.
- 通过CTH/SQOR过度表达或H2S补充恢复H2S或CoQ10H2水平,以防止SA毒性.
- 鉴定出ATF4/CTH/SQOR轴对于维持氧化还原平衡和预防SA诱导的铁亡至关重要.
结论:
- 通过扰乱ATF4/CTH/SQOR轴,SA诱导铁质中介性损伤,导致CoQ10H2降低和氧化还原平衡受损.
- 鉴定的途径代表了减轻SA诱导的毒性的一种新的治疗标.
- 了解这种机制,可以了解铁亡调节和药物诱导的损伤的潜在干预措施.
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