在急性损伤中,STAT3驱动了ACSL4的表达
Virginie Poindessous1, Helene Lazareth1,2,3, Gilles Crambert4,5
1Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Cité, Paris, France.
iScience
|May 27, 2024
概括
长链乙基-CoA合成酶家族4 (ACSF4) 在损伤时激活STAT3信号,但不会导致铁亡. 相反,它在管状上皮细胞中丰富了甘油三,而不是脂.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 长链乙-CoA合成酶家族4 (ACSL4) 代谢多不和脂肪酸 (PUFA),促进铁亡.
- 目前尚不清楚ACSL4和铁死在内质网膜 (ER) 中引起的急性损伤 (AKI) 的作用.
研究的目的:
- 调查ACSL4调节及其对ER压力诱导的AKI期间管状上皮细胞 (TECs) 膜脂质组重塑的影响.
主要方法:
- 利用脂质,分子和细胞生物学技术.
- 采用了由ER压力诱导的AKI的小鼠模型.
主要成果:
- 在ER压力期间,TECs在响应STAT3信号时激活ACSL4.
- 膜脂层重塑有利于PUFA丰富的甘油三,而不是TEC中的PUFA含脂.
- 在这些条件下,ACSL4在TEC中的表达不会导致铁亡.
结论:
- 在TEC中ACSL4的激活是STAT3依赖的,但不仅仅是使细胞对ferroptosis敏感.
- 生物背景显著影响了ACSL4的作用和AKI中的ferroptosis脆弱性.
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