Mitochondria‑associated protein LRPPRC exerts cardioprotective effects against doxorubicin‑induced toxicity, potentially via inhibition of ROS accumulation

Tang,Quan; Xiong,Wei; Ke,Xixian; Zhang,Jian; Xia,Yu; Liu,Daxing

doi:10.3892/etm.2020.9111

Mitochondria‑associated protein LRPPRC exerts cardioprotective effects against doxorubicin‑induced toxicity, potentially via inhibition of ROS accumulation

Authors:
- Quan Tang
- Wei Xiong
- Xixian Ke
- Jian Zhang
- Yu Xia
- Daxing Liu
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Affiliations: Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China
Published online on: August 7, 2020 https://doi.org/10.3892/etm.2020.9111
Pages: 3837-3845
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Doxorubicin (DOX) has been widely employed to treat cancer, particularly solid tumors and hematological malignancies, owing to its high efficacy; however, chemotherapy has been indicated to be cardiotoxic and induce adverse effects, including mitochondrial dysfunction and DNA damage, which limits its application. The mitochondria‑associated protein leucine‑rich pentatricopeptide repeat‑containing (LRPPRC) has been reported to serve critical regulatory roles in physiological processes via regulating mitochondrial function. The aim of the present study was to investigate the possible protective effects of LRPPRC against DOX‑induced cardiac injury. In a DOX‑induced cardiotoxicity model in H9C2 cells, LRPPRC was indicated to be transcriptionally upregulated and stabilize Bcl‑2 and Bax. LRPPRC overexpression exhibited protective effects against proliferation and both apoptotic and non‑apoptotic cell death following DOX treatment, but not under normal conditions. It was additionally observed that overexpressed LRPPRC reversed the decreases in ATP synthesis, mitochondrial mass and transcriptional activity, which were induced by DOX exposure. Overexpressed LRPPRC also decreased the accumulation of reactive oxygen species (ROS) under DOX treatment and inhibited cell death to a similar extent as N‑acetyl‑L‑cysteine, which is a known ROS scavenger, indicating that LRPPRC potentially exerts protective effects via inhibiting ROS accumulation. Moreover, LRPPRC overexpression protected H9C2 cells against oxidative stress induced by H2O2, which also indicated its ROS‑scavenging function. The present study demonstrated for the first time, to the best of our knowledge, that DOX‑induced LRPPRC may exert cardioprotective effects via inhibiting ROS accumulation, thereby maintaining mitochondrial function.

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