依赖FTMT的线粒对于心脏纤维细胞中铁灭症抵抗至关重要
Cheng-Zhang Xu1, Qing-Yuan Gao1, Guang-Hao Gao1
1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Biochimica et biophysica acta. Molecular cell research
|August 21, 2024
概括
高葡萄糖会诱导心肌细胞中的铁亡,而不是心脏纤维细胞. 心脏纤维细胞通过由FOXA1.1调节的线粒体铁素 (FTMT) 依赖于线粒体铁素的线粒细胞衰变抵抗铁.
科学领域:
- 细胞代谢的细胞代谢.
- 心血管研究的心血管研究.
- 自和铁灭菌是自和铁灭菌.
背景情况:
- 细胞应激反应,包括线粒,在铁灭过程中至关重要.
- 了解心脏细胞中高葡萄糖的代谢适应是必不可少的.
研究的目的:
- 研究高葡萄糖对心肌细胞 (CMs) 和心脏纤维细胞 (CFs) 铁亡的影响.
- 阐明潜在的机制,包括代谢途径和线粒细胞衰变.
主要方法:
- 在高葡萄糖条件下分析糖解,线粒体氧化酸化 (OXPHOS) 和线粒体衰变.
- 评估铁,线粒体铁素 (FTMT),NCOA4和FOXA1的表达.
- 对FTMT的基因沉默和对FOXA1与FTMT促进体结合的研究.
主要成果:
- 高葡萄糖诱导了CMs中的铁亡,但在CF中产生了耐药性.
- 在高葡萄糖下,CFs表现出增加的葡萄糖分解,增强的线粒,以及高调的FTMT和FOXA1.
- 福克斯A1直接与FTMT促进体结合,在CF中驱动FTMT转录和随后的线粒.
结论:
- 高葡萄糖通过FOXA1.1.促进心脏纤维细胞中FTMT依赖的线粒和铁灭的抵抗力.
- 这项研究揭示了在高血糖压力下心脏纤维细胞中代谢适应和细胞存活的新奇机制.
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