梅特福明通过促进NETosis来应对脏ferroptosis来增强脏毒性
Zhaoxian Cai1,2, Xiaotian Wu1, Zijun Song1
1The Second Affiliated Hospital, The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Cancer Center, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Cell discovery
|October 17, 2023
概括
在小鼠中,甲意外地恶化了急性损伤 (AKI) 和死亡率,因为它诱导了铁亡和中性粒细胞NETosis. 阻断铁或中性粒细胞,并减少铁,防止这种甲福林诱导的毒性.
科学领域:
- 老年病学和科.
- 毒品引起的伤害机制 毒品引起的伤害机制
背景情况:
- 人口老龄化增加了与年龄有关的疾病的负担.
- 甲胺在衰老和临床前模型中显示出好处,但其对脏衰老的影响尚不清楚.
- 功能随着年龄的增长而下降,使其易受伤害.
研究的目的:
- 调查甲福明对急性损伤 (AKI) 的作用.
- 阐明甲福林在衰老过程中对脏健康的影响背后的机制.
主要方法:
- 在接受AKI和甲福明治疗的小鼠中进行单细胞转录组学分析.
- 研究了编程细胞死亡途径,特别是铁亡.
- 研究了中性粒细胞和中性粒细胞细胞外陷形成 (NETosis) 的作用.
- 评估铁含量和特定分子标 (CXCR4) 的影响.
主要成果:
- 甲胺在小鼠中加剧了AKI并增加了死亡率,即使在低剂量中.
- 甲胺治疗导致关细胞通过铁亡和中性粒细胞扩张死亡.
- 阻断铁亡或消耗保护于甲福林诱导损伤的中性粒细胞.
- 甲胺-铁-NGAL复合物通过CXCR4调解了中性粒细胞迁移和NETosis,加剧了AKI.
- 降低铁含量表明对甲胺触发的AKI有保护作用.
结论:
- 矛盾的是,甲福明可以通过铁死和中性粒细胞介导的NETosis恶化急性损伤.
- 铁在甲胺诱导的毒性中起着至关重要的作用.
- 向铁,中性粒细胞或铁代谢可能为甲胺相关损伤提供治疗策略.
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