TRAP1 attenuates H9C2 myocardial cell injury induced by extracellular acidification via the inhibition of MPTP opening

Extracellular acidification leads to cardiac dysfunction in numerous diseases. Mitochondrial dysfunction plays an important role in this process. However, the mechanisms through which extracellular acidification induces mitochondrial dysfunction remain unclear. Tumor necrosis factor receptor-associa...

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Bibliographic Details
Published in:International journal of molecular medicine 2020-08, Vol.46 (2), p.663-674
Main Authors: Zhang, Lingxiao, Liu, Lerong, Li, Xia, Zhang, Xing, Zhao, Jiangpei, Luo, Yuanyuan, Guo, Xiangyu, Zhao, Tongfeng
Format: Article
Language:English
Subjects:
Acidosis
Antibodies
Apoptosis
Biotechnology
Cardiomyocytes
Cell culture
Flow cytometry
Hypoxia
Infections
Ischemia
Oxidative stress
Permeability
Proteins
Tumor necrosis factor
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Summary:Extracellular acidification leads to cardiac dysfunction in numerous diseases. Mitochondrial dysfunction plays an important role in this process. However, the mechanisms through which extracellular acidification induces mitochondrial dysfunction remain unclear. Tumor necrosis factor receptor-associated protein 1 (TRAP1) maintains mitochondrial function and cell viability in tumor and non-tumor cells. In the present study, extracellular acidification was found to induce H9C2 cell apoptosis, mitochondrial dysfunction and TRAP1 expression. The overexpression of TRAP1 attenuated H9C2 cell injury, while the silencing of TRAP1 exacerbated it. Moreover, mitochondrial permeability transition pore (MPTP) opening, which is associated with the mitochondrial apoptotic pathway and cell death, was also increased in acidic medium. The overexpression of TRAP1 inhibited MPTP opening, while the silencing of TRAP1 promoted it. The protective effect of TRAP1 on cardiomyocytes was abolished by the addition of a specific MPTP opening promoter. Similarly, a specific MPTP opening inhibitor reversed cell injury by silencing TRAP1. Taken together, the findings of the present study demonstrate that TRAP1 attenuates H9C2 cell injury induced by extracellular acidification by inhibiting MPTP opening.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2020.4631