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

Abstract

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.

Nuclear respiratory factor 1 protects H9C2 cells against hypoxia‐induced apoptosis via the death receptor pathway and mitochondrial pathway

“…MMP is also a hallmark of mitochondrial function and cellular metabolic activity, such as oxidative phosphorylation and electron transport. Similar to our previous study (Niu et al, 2019), the present study showed that NRF-1 overexpression remarkably inhibited ROS generation and MMP loss in hypoxia-treated H9C2 cells, suggesting that NRF-1 has a protective effect against oxidative stress and mitochondrial dysfunction. These results are also consistent with previous reports suggesting that NRF-1 protects against cellular ROS toxicity after ischemic and traumatic brain injury (Hertel et al, 2002), and against mitochondrial dysfunction in 1methyl-4-phenylpyridinium-induced neuronal cells (Piao et al, 2012) and in benzo(a)pyrene-induced human bronchial epithelial cells (Zhang et al, 2011).…”

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

“…Nuclear respiratory factor 1 (NRF1) is a ubiquitous transcription factor related to mitochondrial biogenesis and function and plays a role in apoptosis through the mitochondrial associated genes [150][151][152]. NRF1 interacts with the consensus DNA sequence (YGCGCAYGCGCR) DNA via its two zinc finger domains [153,154].…”

Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

“…Previous studies on NRF-1 have primarily focused on its effect on mitochondrial function and showed that NRF-1 could regulate the expression of mitochondrial respiratory chain complex gene family members, affecting mitochondrial biogenesis, and increase mitochondrial ATP production [47,48]. Reportedly, NRF-1 can signi cantly improve the mitochondrial membrane potential in cardiomyocytes under hypoxia and enhance the mitochondrial respiratory capacity to increase cardiomyocyte viability [5].…”

“…Apoptosis is one of the primary forms of myocardial cell death [3,4], and hypoxia-induced apoptosis is a strong indicator of myocardial damage. In our previous study, the nuclear respiratory factor-1 (NRF-1) was found to alleviate the damage caused to myocardial cells by cobalt chloride, an anoxic chemical agent, by inhibiting apoptosis [5]. NRF-1 is a 68 kDa nuclear transcription regulator that was initially detected in a study on the activation and expression of cytochrome c [6].…”