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

Zhang,Lingxiao; Liu,Lerong; Li,Xia; Zhang,Xing; Zhao,Jiangpei; Luo,Yuanyuan; Guo,Xiangyu; Zhao,Tongfeng

doi:10.3892/ijmm.2020.4631

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

Authors:
- Lingxiao Zhang
- Lerong Liu
- Xia Li
- Xing Zhang
- Jiangpei Zhao
- Yuanyuan Luo
- Xiangyu Guo
- Tongfeng Zhao
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Affiliations: Department of Endocrinology, The Sixth Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Neurology, The Sixth Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Guangdong‑Hongkong‑Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: June 4, 2020 https://doi.org/10.3892/ijmm.2020.4631
Pages: 663-674
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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