Effects of nuclear respiratory factor‑1 on apoptosis and mitochondrial dysfunction induced by cobalt chloride in H9C2 cells

Niu,Nan; Li,Zihua; Zhu,Mingxing; Sun,Hongli; Yang,Jihui; Xu,Shimei; Zhao,Wei; Song,Rong

doi:10.3892/mmr.2019.9839

Effects of nuclear respiratory factor‑1 on apoptosis and mitochondrial dysfunction induced by cobalt chloride in H9C2 cells

Authors:
- Nan Niu
- Zihua Li
- Mingxing Zhu
- Hongli Sun
- Jihui Yang
- Shimei Xu
- Wei Zhao
- Rong Song
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Affiliations: College of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China, School of Pharmacy, Tsinghua University, Beijing 100084, P.R. China, Department of Critical Care Medicine, The Fifth Hospital of the Chinese People's Liberation Army, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
Published online on: January 10, 2019 https://doi.org/10.3892/mmr.2019.9839
Pages: 2153-2163
Copyright: © Niu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypoxia‑induced apoptosis occurs in various diseases. Cobalt chloride (CoCl2) is a hypoxia mimic agent that is frequently used in studies investigating the mechanisms of hypoxia. Nuclear respiratory factor‑1 (NRF‑1) is a transcription factor with an important role in the expression of mitochondrial respiratory and mitochondria‑associated genes. However, few studies have evaluated the effects of NRF‑1 on apoptosis, particularly with regard to damage caused by CoCl2. In the present study, the role of NRF‑1 in mediating CoCl2‑induced apoptosis was investigated using cell viability analysis, flow cytometry, fluorescence imaging, western blotting analysis, energy metabolism analysis and reverse transcription‑quantitative polymerase chain reaction. The present results revealed that the apoptosis caused by CoCl2 could be alleviated by NRF‑1. Furthermore, overexpression of NRF‑1 increased the expression of B‑cell lymphoma‑2, hypoxia inducible factor‑1α and NRF‑2. Also, cell damage induced by CoCl2 may be associated with depolarization of mitochondrial membrane potential, and NRF‑1 suppressed this effect. Notably, the oxygen consumption rate (OCR) was reduced in CoCl2‑treated cells, whereas overexpression of NRF‑1 enhanced the OCR, suggesting that NRF‑1 had protective effects. In summary, the present study demonstrated that NRF‑1 protected against CoCl2‑induced apoptosis, potentially by strengthening mitochondrial function to resist CoCl2‑induced damage to H9C2 cells. The results of the present study provide a possible way for the investigation of myocardial diseases.

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