Overexpressed UCP2 regulates mitochondrial flashes and reverses lipopolysaccharide-induced cardiomyocytes injury

Background: Mitochondrial flashes (mitoflashes) are transient signals from transient bursts of reactive oxygen species (ROS) and changes in pH that occur in certain physiological or pathological conditions. Mitoflashes are closely related to metabolism, cell differentiation, stress response, diseases, and aging. Sepsis can trigger mitochondrial dysfunction in myocardial cells, which leads to ROS overproduction, while uncoupling protein 2 (UCP2) can reduce ROS production. This study aims to observe whether UCP2 overexpression can regulate the frequency of mitoflashes in cardiomyocytes during sepsis and thereby play a protective role. Methods: A cell model for sepsis-induced myocardial damage was established using lipopolysaccharide (LPS). UCP2 overexpression in cardiomyocytes was achieved by adenovirus transfection. Creatinine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor (TNF-α), and interleukin (IL-6) activities were detected, and mitochondrial membrane potentials (MMP) were measured. The frequency of mitoflashes in cardiomyocytes was observed. Results: With LPS stimulation, mitoflashes in cardiomyocytes increased significantly, and the MMP was damaged. Additionally, significant increases in CK, LDH, TNF-α, and IL-6 expression levels were observed. UCP2 overexpression can significantly reverse myocardial cell injuries that result from LPS stimulation. Compared with the LPS group, the LPS+UCP2 overexpression group showed a decrease in mitoflash frequency, an improved MMP, and decreases in CK, LDH, TNF-α, and IL-6 expression levels. Conclusion: This study is the first to demonstrate the function of UCP2 overexpression in protecting the myocardium by regulating mitoflash frequency and reversing sepsis-induced myocardial injuries.