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

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

  • Biol Direct. 2024 Aug 2;19(1):62. doi: 10.1186/s13062-024-00505-x.
Pengfei Wang 1,  Xiaohua Guo 1,  Hongchao Wang 1,  Lijie Wang 1,  Meifang Ma 1 2,  Bingyan Guo 3 4
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China.
  • 2 Handan Central Hospital, Handan, 056000, China.
  • 3 Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China. guobingyan@hebmu.edu.cn.
  • 4 Hebei Key Laboratory of Laboratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China. guobingyan@hebmu.edu.cn.
PMID: 39095871 DOI: 10.1186/s13062-024-00505-x
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.

Keywords

AMPK; Diabetic cardiomyopathy; Ferroptosis; NRF2; Neuregulin-4.

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