U(VI) exposure induces apoptosis and pyroptosis in RAW264.7 cells

U(VI) pollution has already led to serious harm to the environment and human health with the increase of human activities. The viability of RAW264.7 cells was assessed under various U(VI) concentration stress for 24 and 48 h. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD) activities of RAW264.7 cells under U(VI) stress were measured. The results showed that U(VI) decreased cell activity, induced intracellular ROS production, abnormal MMP, and increased SOD activity. The flow cytometry with Annexin-V/PI double labeling demonstrated that the rate of late apoptosis increased with the increase of U(VI) concentration, resulting in decreased Bcl-2 expression and increased Bax expression. The morphology of RAW264.7 cells dramatically changed after 48 h U(VI) exposure, including the evident bubble phenomenon. Besides, U(VI) also increased the proportion of LDH releases and increased GSDMD, and Ras, p38, JNK, and ERK1/2 protein expression, which indicated that the MAPK pathway was also involved. Therefore, U(VI) ultimately led to apoptosis and pyroptosis in RAW264.7 cells. This study offered convincing proof of U(VI) immunotoxicity and established the theoretical framework for further fundamental studies on U(VI) toxicity.