在心脏缺血再灌注损伤中，YTHDF2 通过降解 SLC7A11 促进心脏铁素体生成

IF 5.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Antioxidants & redox signaling Pub Date : 2024-06-01 Epub Date: 2023-11-10 DOI:10.1089/ars.2023.0291

Ping Pang, Wei Si, Han Wu, Jiaming Ju, Kuiwu Liu, Chunlei Wang, Yingqiong Jia, Hongtao Diao, Linghua Zeng, Weitao Jiang, Yang Yang, Yuting Xiong, Xue Kong, Zhengwei Zhang, Feng Zhang, Jinglun Song, Ning Wang, Baofeng Yang, Yu Bian

引用次数: 0

摘要

目的：心肌缺血再灌注（I/R）损伤会导致心肌细胞死亡并危及人类健康。N6-甲基腺苷（m6A）甲基化在心血管疾病中起着关键作用。m6A 阅读器 YTHDF2 能识别 m6A 修饰的 RNA 并促进靶 RNA 降解。因此，我们假设 YTHDF2 通过调节 RNA 的稳定性来影响 I/R 损伤。结果在I/R小鼠和低氧-复氧（H/R）诱导的心肌细胞中，YTHDF2的信使RNA（mRNA）和蛋白水平均上调。沉默内源性 YTHDF2 可减轻 I/R 小鼠的心功能障碍并缩小梗死范围，而强迫表达 YTHDF2 则会加重这些不良病理过程。同样，沉默 YTHDF2 对暴露于 H/R 和麦拉宁的心肌细胞也有保护作用。此外，RNA-Seq和RNA结合蛋白免疫沉淀（RIP）发现，YTHDF2能识别铁变态反应相关基因溶质运载家族7成员11（SLC7A11）mRNA的m6A修饰位点，从而促进其在体内和体外的降解。沉默 YTHDF2 后，抑制 SLC7A11 会损害 I/R 小鼠的心脏功能、增加梗死面积和乳酸脱氢酶（LDH）的释放。与 SLC7A11 特异性 siRNA（si-SLC7A11）联合转染可逆转 si-YTHDF2 对 H/R 损伤的有益影响，因为 Si-YTHDF2 会大大加剧铁变态反应和活性氧的产生。创新与结论：沉默YTHDF2的心脏保护作用是通过增加SLC7A11的稳定性和表达、减少铁卟啉沉着来实现的，为治疗缺血性心脏疾病提供了新的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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YTHDF2 Promotes Cardiac Ferroptosis via Degradation of SLC7A11 in Cardiac Ischemia-Reperfusion Injury.

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来源期刊

Antioxidants & redox signaling 生物-内分泌学与代谢

CiteScore

14.10

自引率

1.50%

发文量

170

审稿时长

3-6 weeks

期刊介绍： Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology