Neuregulin-4 protects cardiomyocytes against high-glucose-induced ferroptosis via the AMPK/NRF2 signalling pathway.

IF 5.7 2区生物学 Q1 BIOLOGY

Biology Direct Pub Date : 2024-08-02 DOI:10.1186/s13062-024-00505-x

Pengfei Wang, Xiaohua Guo, Hongchao Wang, Lijie Wang, Meifang Ma, Bingyan Guo

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引用次数: 0

Abstract

Background: High glucose levels are key factors and key contributors to several cardiovascular diseases associated with cardiomyocyte injury. Ferroptosis, which was identified in recent years, is a mode of cell death caused by the iron-mediated accumulation of lipid peroxides. Neuregulin-4 (Nrg4) is an adipokine that has protective effects against metabolic disorders and insulin resistance. Our previous study revealed that Nrg4 has a protective effect against diabetic myocardial injury, and the aim of this study was to investigate whether Nrg4 could attenuate the occurrence of high glucose-induced ferroptosis in cardiomyocytes.

Methods: We constructed an in vivo diabetic myocardial injury model in which primary cardiomyocytes were cultured in vitro and treated with Nrg4. Changes in ferroptosis-related protein levels and ferroptosis-related indices in cardiomyocytes were observed. In addition, we performed back-validation and explored signalling pathways that regulate ferroptosis in primary cardiomyocytes.

Results: Nrg4 attenuated cardiomyocyte ferroptosis both in vivo and in vitro. Additionally, the AMPK/NRF2 signalling pathway was activated during this process, and when the AMPK/NRF2 pathway was inhibited, the beneficial effects of Nrg4 were attenuated.

Conclusion: Nrg4 antagonizes high glucose-induced ferroptosis in cardiomyocytes via the AMPK/NRF2 signalling pathway.

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Neuregulin-4通过AMPK/NRF2信号通路保护心肌细胞免受高血糖诱导的铁变态反应。

背景：高血糖是导致与心肌细胞损伤有关的多种心血管疾病的关键因素和重要诱因。近年来发现的铁过氧化是一种由铁介导的脂质过氧化物积累引起的细胞死亡模式。Neuregulin-4（Nrg4）是一种脂肪因子，对代谢紊乱和胰岛素抵抗具有保护作用。我们之前的研究发现，Nrg4 对糖尿病心肌损伤有保护作用，本研究旨在探讨 Nrg4 是否能减轻高糖诱导的心肌细胞铁变态反应的发生：方法：我们构建了一个体内糖尿病心肌损伤模型，在体外培养原代心肌细胞并用Nrg4处理。我们观察到了心肌细胞中与铁变态反应相关的蛋白水平和铁变态反应相关指数的变化。此外，我们还进行了反向验证，并探索了调控原代心肌细胞中铁细胞凋亡的信号通路：结果：Nrg4 在体内和体外均可减轻心肌细胞的铁突变。此外，在这一过程中，AMPK/NRF2 信号通路被激活，当 AMPK/NRF2 通路被抑制时，Nrg4 的有益作用就会减弱：结论：Nrg4可通过AMPK/NRF2信号通路拮抗高糖诱导的心肌细胞铁突变。

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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来源期刊

Biology Direct 生物-生物学

CiteScore

6.40

自引率

10.90%

发文量

审稿时长

7 months

期刊介绍： Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.