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Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway

  • Authors:
    • Yunhui Guo
    • Zhiping Li
    • Canxia Shi
    • Jia Li
    • Meng Yao
    • Xia Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 999-1008
    |
    Published online on: August 17, 2017
       https://doi.org/10.3892/ijmm.2017.3101
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Abstract

Trichostatin A (TSA), a histone deacetylase inhibitor, is widely used as an anticancer drug. Recently, TSA has been shown to exert a protective effect on ischemia/reperfusion (I/R) injury; however, the underlying mechanisms remain unclear. Forkhead box O3a (FoxO3a), a unique FoxO family member, has been shown to attenuate myocardial injury by increasing resistance to oxidative stress in mice. The present study aimed to investigate whether TSA exerts its cardioprotective effects through the FoxO3a signaling pathway. For this purpose, healthy male Wistar rats were pre-treated with TSA for 5 days before they were subjected to ligation/relaxation of the left anterior descending branch of the coronary artery and to 30 min of ischemia, followed by 24 h of reperfusion. The activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and superoxide diamutase (SOD), as well as the malondialdehyde (MDA) levels were examined. The H9c2 rat myocardial cell line was cultured in 10% FBS-containing DMEM for 24 h. The cells were incubated with/without TSA (50 nmol/l) for 1 h and then incubated with/without H2O2 (400 µM) for 2 h. Reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) were measured by probe staining in the H9c2 cells. The expression of FoxO3a, mitochondrial SOD2 and catalase was quantified by western blot analysis. The levels of H3 and H4 acetylation of the FoxO3a promoter region were examined by chromatin immunoprecipitation assay. TSA significantly reduced the myocardial infarct size and the activities of serum LDH, AST and CK in the rats. TSA also decreased the levels of MDA and increased the activities of SOD in the myocardial tissue of the rats. Consistent with the reduced injury to the TSA-treated rats, TSA significantly reduced the H2O2-induced levels of ROS and increased Δψm. In addition, TSA increased the expression of FoxO3a, SOD2 and catalase, which may be related to increasing the level of H4 acetylation of the FoxO3a promoter region. Our results thus revealed that TSA protected the myocardium from oxidative stress-mediated damage by increasing H4 acetylation of the FoxO3a promoter region, and the expression of FoxO3a, SOD2 and catalase.
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Copy and paste a formatted citation
Spandidos Publications style
Guo Y, Li Z, Shi C, Li J, Yao M and Chen X: Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway. Int J Mol Med 40: 999-1008, 2017.
APA
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., & Chen, X. (2017). Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway. International Journal of Molecular Medicine, 40, 999-1008. https://doi.org/10.3892/ijmm.2017.3101
MLA
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., Chen, X."Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway". International Journal of Molecular Medicine 40.4 (2017): 999-1008.
Chicago
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., Chen, X."Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway". International Journal of Molecular Medicine 40, no. 4 (2017): 999-1008. https://doi.org/10.3892/ijmm.2017.3101
Copy and paste a formatted citation
x
Spandidos Publications style
Guo Y, Li Z, Shi C, Li J, Yao M and Chen X: Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway. Int J Mol Med 40: 999-1008, 2017.
APA
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., & Chen, X. (2017). Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway. International Journal of Molecular Medicine, 40, 999-1008. https://doi.org/10.3892/ijmm.2017.3101
MLA
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., Chen, X."Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway". International Journal of Molecular Medicine 40.4 (2017): 999-1008.
Chicago
Guo, Y., Li, Z., Shi, C., Li, J., Yao, M., Chen, X."Trichostatin A attenuates oxidative stress-mediated myocardial injury through the FoxO3a signaling pathway". International Journal of Molecular Medicine 40, no. 4 (2017): 999-1008. https://doi.org/10.3892/ijmm.2017.3101
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