Regulatory mechanism of downregulation of SOD1 expression on cardiomyocyte function.

BACKGROUND

Many diseases are clinically related to oxidative stress. Obstructive sleep apnea (OSA) is a common disease with oxidative stress in clinical practice, which is mostly associated with cardio-cerebrovascular diseases. It has been shown that the level of oxidative stress increases and the level of antioxidant copper zinc superoxide dismutase (SOD1) decreases in intermittent hypoxia (IH). SOD1 is one of the key antioxidant enzymes in organisms, and it can also be used as a signal transmission controller. Its abnormal expression further affects organ functions, but the specific mechanism is not yet fully clear.

METHODS

We downregulated the SOD1 gene in H9C2 cell line, using high-throughput RNA sequencing (RNA-seq) to find differentially expressed genes (DEGs) related to cardiomyocyte function by using GO and KEGG databases to annotate, enrich and analyze the metabolic pathways of DEGs.

RESULTS

Through the analysis of these functional gene changes, we can understand the regulation of SOD1 downregulation on cardiomyocyte function. The results found 213 DEGs, of which 135 genes were upregulated and 78 genes were downregulated. The upregulated DEGs were mainly enriched in biological processes such as transcriptional regulation and metabolism. The expression levels of EGR1 and NR1D1 exceeded 1 in the samples. EGR1 was reported to be involved in oxidative stress and cardiac hypertrophy, and NR1D1 played an important regulatory role in regulating inflammatory responses and reducing ROS production. The biological processes involved in downregulated DEGs mainly involve metabolism and redox processes. Among them, SCD1 and CCL2 genes were highly expressed among the genes involved in the redox process involved in SOD1. SCD1 is an important player in the regulation of cardiometabolic processes; downregulation of CCL2 reduces atherosclerosis. We found that the TNF signaling pathway, NOD-like receptor signaling pathway, and chemokine signaling pathway, which were enriched in KEGG analysis, were all associated with inflammation, and the CXCL1 and CCL7 genes are all related to inflammation.

CONCLUSION

The gene and signaling pathways involved in oxidative stress and inflammatory response process regulated by SOD1 were demonstrated. SOD1 may affect the function of the heart by affecting myocardial contraction, inflammation, lipid metabolism, and other pathways. It is inferred that they may also play a role in the process of OSA-related myocardial injury, which is worthy of attention and further study.