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Thorac Cardiovasc Surg
DOI: 10.1055/s-0044-1787691
Original Basic Science

DEX Inhibits H/R-induced Cardiomyocyte Ferroptosis by the miR-141-3p/lncRNA TUG1 Axis

Mei Zhu 
1   Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, People's Republic of China
,
Zhiguo Yuan
1   Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, People's Republic of China
,
Chuanyun Wen
1   Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, People's Republic of China
,
Xiaojia Wei
1   Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, People's Republic of China
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Abstract

Background Ferroptosis is emerging as a critical pathway in ischemia/reperfusion (I/R) injury, contributing to compromised cardiac function and predisposing individuals to sepsis and myocardial failure. The study investigates the underlying mechanism of dexmedetomidine (DEX) in hypoxia/reoxygenation (H/R)-induced ferroptosis in cardiomyocytes, aiming to identify novel targets for myocardial I/R injury treatment.

Methods H9C2 cells were subjected to H/R and treated with varying concentrations of DEX. Additionally, H9C2 cells were transfected with miR-141-3p inhibitor followed by H/R treatment. Levels of miR-141-3p, long noncoding RNA (lncRNA) taurine upregulated 1 (TUG1), Fe2+, glutathione (GSH), and malondialdehyde were assessed. Reactive oxygen species (ROS) generation was measured via fluorescent labeling. Expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined using Western blot. The interaction between miR-141-3p and lncRNA TUG1 was evaluated through RNA pull-down assay and dual-luciferase reporter gene assays. The stability of lncRNA TUG1 was assessed using actinomycin D.

Results DEX ameliorated H/R-induced cardiomyocyte injury and elevated miR-141-3p expression in cardiomyocytes. DEX treatment increased cell viability, Fe2+, and ROS levels while decreasing ACSL4 protein expression. Furthermore, DEX upregulated GSH and GPX4 protein levels. miR-141-3p targeted lncRNA TUG1, reducing its stability and overall expression. Inhibition of miR-141-3p or overexpression of lncRNA TUG1 partially reversed the inhibitory effect of DEX on H/R-induced ferroptosis in cardiomyocytes.

Conclusion DEX mitigated H/R-induced ferroptosis in cardiomyocytes by upregulating miR-141-3p expression and downregulating lncRNA TUG1 expression, unveiling a potential therapeutic strategy for myocardial I/R injury.

Keywords

dexmedetomidine - ischemia/reperfusion - myocardial - ferroptosis - miR-141-3p

Authors' Contribution

M. Z.: Guarantor of the integrity of the entire study, contributed to study concepts, study design, data analysis, statistical analysis, manuscript editing, and manuscript review.


Z. Y.: Contributed to the definition of intellectual content and manuscript preparation.


C. W.: Conducted literature research and experimental studies.


X. W.: Contributed to data acquisition.




Publication History

Received: 21 March 2024

Accepted: 17 May 2024

Article published online:
18 June 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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