姜黄素通过Sirt1/AKT/FoxO3a信号通路减弱心肌缺血再灌注诱导的自噬依赖性铁凋亡。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2025-03-01 Epub Date: 2025-01-24 DOI:10.3892/ijmm.2025.5492
Shi-Tao Zhao, Zhi-Cong Qiu, Zhi-Qiang Xu, En-De Tao, Rong-Bin Qiu, Han-Zhi Peng, Lian-Fen Zhou, Rui-Yuan Zeng, Song-Qing Lai, Li Wan
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引用次数: 0

摘要

姜黄素能有效减轻心肌缺血/再灌注损伤(MIRI)。MIRI具有复杂的机制,与自噬依赖性铁下垂有关。因此,本研究旨在确定自噬依赖性铁下垂是否发生在MIRI中,并评估Cur减轻MIRI的机制。研究采用Sprague - Dawley大鼠MIRI模型和H9c2细胞缺氧/再氧化(a/ R)损伤模型。研究Cur预处理对A/R或MIRI诱导的自噬依赖性铁下垂的影响及其分子机制。蛋白表达、溶酶体、活性氧、Fe2+、氧化系统、线粒体功能、分子亚细胞定位和心功能分析将被采用。Cur降低MIRI;改善心肌组织病理学;心肌细胞活力增加;抑制铁下垂、细胞凋亡和自噬;减少梗死面积,维持心功能。MIRI降低沉默信息调节因子1 (Sirt1),降低AKT和叉头盒O3A (FoxO3a)磷酸化,导致FoxO3a进入细胞核,激活自噬相关基因的翻译,诱导铁凋亡、细胞凋亡和自噬。然而,Cur预处理通过Sirt1激活AKT和FoxO3a磷酸化,从而将FoxO3a转运出核,减少自噬相关基因的翻译,减弱MIRI诱导的铁凋亡、细胞凋亡和自噬。值得注意的是,Sirt1的沉默和triciribine(一种AKT抑制剂)的使用都消除了Cur的保护作用。因此,Cur通过Sirt1/AKT/FoxO3a信号传导抑制自噬依赖性铁凋亡,从而维持心肌细胞功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling.

Curcumin (Cur) effectively attenuates myocardial ischemia/reperfusion injury (MIRI). MIRI has a complex mechanism and is associated with autophagy‑dependent ferroptosis. Therefore, the present study aimed to determine whether autophagy‑dependent ferroptosis occurs in MIRI and assess the mechanism of Cur in attenuating MIRI. The study was conducted on a Sprague‑Dawley rat MIRI model and H9c2 cell anoxia/reoxygenation (A/R) injury model. The effect of Cur pretreatment on A/R or MIRI induced autophagy‑dependent ferroptosis and its molecular mechanism were investigated. Protein expression, lysosomal, reactive oxygen species, Fe2+, oxidative systems, mitochondrial function, subcellular localization of molecules, and cardiac function assays will be employed. Cur decreased MIRI; improved myocardial histopathology; increased cardiomyocyte viability; inhibited ferroptosis, apoptosis and autophagy; reduced infarct size and maintained cardiac function. MIRI decreased silent information regulator 1 (Sirt1), decreased AKT and forkhead box O3A (FoxO3a) phosphorylation, leading to FoxO3a entry into the nucleus to activate translation of autophagy‑related genes and inducing ferroptosis, apoptosis and autophagy. However, Cur pretreatment activated AKT and FoxO3a phosphorylation via Sirt1, thereby transporting FoxO3a out of the nucleus, reducing autophagy‑related gene translation and attenuating MIRI‑induced ferroptosis, apoptosis and autophagy. Of note, the silencing of Sirt1 and administration of triciribine (an AKT inhibitor) both eliminated the protective effect of Cur. Thus, Cur maintained cardiomyocyte function by inhibiting autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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