Role of the ROS/NLRP3/caspase-1 pathway in NiSO4-induced cellular pyroptosis and apoptosis in H9c2 cells

Abstract

According to comprehensive research, the cardiovascular system is damaged by nickel exposure. The present study selected rat cardiomyocytes (H9c2 cells) and subjected them to varying doses of sodium nickel sulfate (NiSO₄) for 24 hours to better understand the mechanism of cardiovascular damage caused by NiSO₄ exposure. The relevant indicators were detected employing biochemical analysis, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot, and flow cytometry was used to detect the cell apoptosis rate. The study revealed that the survival rate of H9c2 cells fell significantly when the concentration of NiSO₄ exposure rose. Moreover, it caused oxidative stress in H9c2 cells by raising the expression of reactive oxygen species and the concentration of LDH in the cell supernatants. After NiSO₄ exposure, the levels of ASC, NLRP3, gasdermin D, and caspase-1 in H9c2 cells increased, suggesting that H9c2 cells underwent pyroptosis induced by NiSO₄. In addition, NiSO₄ exposure also led to inflammation, with increased levels of interleukin [IL]-18, IL-1β. After adding the antioxidant N-Acetyl-L-cysteine (NAC), the level of ROS indicated that the oxidative stress level in H9c2 cells was reduced, western blot inhibited inflammation, the level of pyroptosis was reduced, and the activity of the NLRP3/caspase1 signaling pathway was reduced. To examine the connection between pyroptosis and apoptosis, the cells were treated with the caspase1 inhibitor Z-YVAD-Fluoromethyl Ketone (Z-YVAD-FMK, YVAD), which resulted in a significant decrease in the rate of cell apoptosis as well as a reduction in the activity of the related protein in the signaling pathway, which in turn decreased the level of pyroptosis. NiSO₄ could induce pyroptosis in H9c2 cells through the ROS/NLRP3/caspase-1 axis. Furthermore, NiSO₄-induced apoptosis and pyroptosis were found to be reduced by the addition of the caspase-1 inhibitor.