Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing ROS, ERS and Pannexin-1-mediated ferroptosis

Authors

DOI:

https://doi.org/10.17305/bb.2022.8846

Keywords:

Diabetic cardiomyopathy, Spermidine, Ferroptosis, Pannexin-1, P2X7

Abstract

Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine has cardioprotective effects. Here, we verified the hypothesis of spermidine's protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of spermidine. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous spermidine could improve cardiac functions and reduce the deposition of collagens, myocardial damage, reactive oxygen species (ROS) levels and endoplasmic reticulum stress (ERS) in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes displayed ferroptosis and then activated Pannexin-1 expression, which resulted in the increase of the extracellular adenosine triphosphate (ATP). Subsequently, increased ATP as a paracrine molecule combined to purinergic receptor P2X7 (P2X7) to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, spermidine could reverse these molecular processes. Our findings indicate an important new mechanism for DCM, and suggest spermidine have potential applicability to protect against deterioration of cardiac function with DCM.

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Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing ROS, ERS and Pannexin-1-mediated ferroptosis

Published

2023-03-18

How to Cite

1.
Sun J, Xu J, Liu Y, Lin Y, Wang F, Han Y, Zhang S, Gao X, Xu C, Yuan H. Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing ROS, ERS and Pannexin-1-mediated ferroptosis. Biomol Biomed [Internet]. 2023Mar.18 [cited 2023Mar.21];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/8846

Issue

Section

Pharmacology