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Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway

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Abstract

Background

Myocardial ischemia/reperfusion injury (MIRI) seriously threatens the health of people. The mitochondrial dysfunction in cardiomyocytes can promote the progression of MIRI. Dexmedetomidine (Dex) could alleviate the myocardial injury, which was known to reverse mitochondrial dysfunction in lung injury. However, the function of Dex in mitochondrial dysfunction during MIRI remains unclear.

Objective

To assess the function of Dex in mitochondrial dysfunction during MIRI.

Methods

To investigate the function of Dex in MIRI, H9C2 cells were placed in condition of hypoxia/reoxygenation (H/R). CCK8 assay was performed to test the cell viability, and the mitochondrial membrane potential was evaluated by JC-1 staining. In addition, the binding relationship between Sirt3 and Prdx3 was explored by Co-IP assay. Furthermore, the protein expressions were examined using western blot.

Results

Dex could abolish H/R-induced mitochondrial dysfunction in H9C2 cells. In addition, H/R treatment significantly inhibited the expression of Sirt3, while Dex partially restored this phenomenon. Knockdown of Sirt3 or Prdx3 obviously reduced the protective effect of Dex on H/R-induced mitochondrial injury. Meanwhile, Sirt3 could enhance the function of Prdx3 via deacetylation of Prdx3.

Conclusion

Dex was found to attenuate H/R-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. Thus, this study might shed new lights on exploring new strategies for the treatment of MIRI.

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Data availability

The supplementary materials_raw data were shown in: https://osf.io/hn9z6/; DOI: https://doi.org/10.17605/OSF.IO/HN9Z6.

Abbreviations

Dex:

Dexmedetomidine

Sirt3:

Sirtuin-3

Prdx3:

Peroxiredoxin-3

MMP:

Mitochondrial membrane potential

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Funding

This work was supported by the Scientific Research Project of Heilongjiang Health Commission (20210404110049) and Basic scientific research funds for colleges and universities in Heilongjiang Province (2023-KYYWF-0636).

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, No.348, Dexiang Street, Xiangyang District, Jiamusi, 154002, Heilongjiang Province, People’s Republic of China

    Qingyun Tan, Qingdong Wang & Li Gao

  2. Department of Anesthesiology, Shenzhen Baoan Hospital of TCM, Shenzhen, 518133, Guangdong Province, People’s Republic of China

    Wenming Dong

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  1. Qingyun Tan
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Correspondence to Qingdong Wang or Li Gao.

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Tan, Q., Dong, W., Wang, Q. et al. Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. DARU J Pharm Sci (2024). https://doi.org/10.1007/s40199-024-00504-3

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