转硫代谢对于静止内皮细胞中铁灭性耐药性至关重要
Roxana Elena Oberkersch1, Jacopo Lidonnici1, Sebastiano Andreuzza1
1Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padua, Padua, Italy.
Cell death & disease
|December 20, 2025
概括
增殖性内皮细胞 (PECs) 使用细胞外囊进行铁灭保护,而静止细胞 (QECs) 激活转硫路径. 缺氧将PEC转移到类似QEC的耐铁的状态.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 生理学 生理学 生理学
背景情况:
- 血管新生包括内皮细胞的增殖和代谢变化.
- 铁,一种依赖于铁的细胞死亡,影响血管生成.
- 通过谷氨 (GSH) 和GPX4的囊代谢调节铁.
研究的目的:
- 研究在增殖 (PECs) 和静止 (QECs) 内皮细胞中囊/GSH/GPX4轴的差异调节.
- 确定这些细胞是如何保护自己免受铁灭的.
- 探索低氧在这种调节中的作用.
主要方法:
- 在不同条件下培养PEC和QEC的细胞培养 (囊可用性,缺氧).
- 对氨酸摄取,GSH合成和TSP活动的分析.
- 对铁亡标记物和NRF2表达的评估.
- 在体内研究使用视网膜血管生成模型与xCT抑制.
主要成果:
- PECs依赖于细胞外的囊来进行GSH合成和预防ferroptosis.
- QECs激活了转硫路径 (TSP) 以抵御囊饥饿的弹性.
- 慢性缺氧诱导PECs中的铁灭症抵抗,通过NRF2-介导的TSP激活模仿QECs.
- 在体内抑制xCT会在血管生成过程中导致内皮细胞死亡.
结论:
- PEC和QEC表现出不同的氨酸代谢策略来控制铁亡.
- 囊/GSH/GPX4轴根据内皮细胞状态进行差异调节.
- 针对这一轴为血管生成相关疾病提供了潜在的治疗策略.
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