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

Hypoxia-induced apoptosis occurs in various diseases. Cobalt chloride (CoCl(2)) 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 CoCl(2). In the present study, the role of NRF-1 in mediating CoCl(2)-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 CoCl(2) 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 CoCl(2) may be associated with depolarization of mitochondrial membrane potential, and NRF-1 suppressed this effect. Notably, the oxygen consumption rate (OCR) was reduced in CoCl(2)-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 CoCl(2)-induced apoptosis, potentially by strengthening mitochondrial function to resist CoCl(2)-induced damage to H9C2 cells. The results of the present study provide a possible way for the investigation of myocardial diseases.