Overexpression of COX5A protects H9c2 cells against doxorubicin-induced cardiotoxicity.

Abstract

Mitochondrial dysfunction plays a pivotal role in doxorubicin (DOX)-induced cardiomyopathy. Cytochrome c oxidase subunit 5A (COX5A) is a nuclear-encoded subunit of the terminal oxidase involved in mitochondrial electron transport. Although COX5A appears to play a key role in modulating the physiological activity of COX and involve in energy metabolism, the involvement of COX5A in DOX-induced cardiotoxicity remains unclear. In this study, we showed that COX5A was significantly downregulated by DOX treatment of H9c2 cells. Overexpression of COX5A in H9c2 cells effectively attenuated DOX-induced apoptosis. Meanwhile, DOX-induced decrease in mitochondrial membrane potential could be reserved by COX5A overexpression. Furthermore, COX5A overexpression relieved the DOX-induced suppression of mitochondrial respiration, due an increase in basal respiration, maximal respiration, ATP production, and spare respiratory capacity. These findings indicate that up-regulation of COX5A may inhibit the apoptosis and alleviate the mitochondrial dysfunction of DOX-treated H9c2 cells. Thus, COX5A may have potential for clinical use as a therapeutic target in DOX-induced cardiotoxicity.

• Authors: Peipei Zhang, Zhangwei Chen, Danbo Lu, Yuan Wu, Mengkang Fan, Juying Qian, Junbo Ge
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 524 Issue 1 Pg. 43-49 (03 26 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 31980176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Doxorubicin
• COX5A protein, human
• Electron Transport Complex IV
• DNA Nucleotidylexotransferase

Topics

• Antibiotics, Antineoplastic (adverse effects)
• Apoptosis (drug effects)
• Cardiotoxicity (prevention & control)
• DNA Nucleotidylexotransferase (metabolism)
• Doxorubicin (adverse effects)
• Electron Transport
• Electron Transport Complex IV (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Membrane Potential, Mitochondrial
• Mitochondria (metabolism)
• Mitochondria, Heart (metabolism)
• Myocytes, Cardiac (cytology, metabolism)
• Oxidative Phosphorylation
• Signal Transduction