Thioredoxin Reductase 2 Synergizes with Cytochrome c, Somatic to Alleviate Doxorubicin-Induced Oxidative Stress in Cardiomyocytes and Mouse Myocardium.

Chuyun Li, Hengli Lai, Xinyong Cai, Yuanyuan Liu, Lang Hong, Xiao Huang, Liang Shao

International heart journal 2023 Mar 31

filter terms:

Doxorubicin (DOX) may cause multiple side effects, which include cardiotoxicity. Hence, to ascertain the impact of thioredoxin reductase 2 (TXNRD2) and cytochrome c, somatic (CYCS) on DOX-induced oxidative stress (OS) in cardiomyocytes and mouse myocardium, this study was implemented. DOX was utilized to treat cardiomyocytes and mice, and TXNRD2 and CYCS expression in cell supernatant and mouse myocardial tissues was detected. TXNRD2 and/or CYCS were overexpressed in DOX-induced cardiomyocytes and mice. In cardiomyocytes, cell viability and the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) were measured. In mice, pathologic changes of the heart, ejection fraction (EF), fractional shortening (FS), and heart weight (HW) /tibial length (TL) ratio, and the contents of lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI) were analyzed. To assess the binding between TXNRD2 and CYCS, coimmunoprecipitation and glutathione S-transferase pull-down assays were performed. TXNRD2 and CYCS were downregulated in DOX-treated cardiomyocytes and mice. Mechanistically, TXNRD2 interacted with CYCS. Overexpression of TXNRD2 or CYCS augmented viability and SOD, CAT, and GSH levels but reduced ROS and MDA contents in DOX-induced cardiomyocytes, which was further facilitated by simultaneous overexpression of TXNRD2 or CYCS. Moreover, TXNRD2 or CYCS upregulation improved the pathologic changes in myocardial tissues, along with increases in EF, FS, and HW/TL ratio of the heart and SOD, CAT, and GSH levels and decreases in LDH, CK-MB, cTnI, ROS, and MDA levels. TXNRD2 coordinated with CYCS to alleviate DOX-induced OS in cardiomyocytes and mouse myocardium.

Citation

Chuyun Li, Hengli Lai, Xinyong Cai, Yuanyuan Liu, Lang Hong, Xiao Huang, Liang Shao. Thioredoxin Reductase 2 Synergizes with Cytochrome c, Somatic to Alleviate Doxorubicin-Induced Oxidative Stress in Cardiomyocytes and Mouse Myocardium. International heart journal. 2023 Mar 31;64(1):60-70