ROS/AMPK Signaling Is Involved In Cell Apoptosis Induced By Copper Ion And Simulated Space Environment In Human B Lymphoblasts

AMPK plays a key role in energy metabolism, and it is also involved in diverse cell signaling pathways, such as apoptosis. Our previous study demonstrated that reactive oxygen species (ROS) were involved in cell apoptosis induced by Cu2+ and simulated space environment. Therefore this study focused whether AMPK is involved in these processes in human B lymphoblasts.Our data showed that:1) The phosphorylation of AMPK could be induced by Cu2+ in human B lymphoblast cells, in a time-and concentration-dependent manner. Cu2+ also triggered intracellular ROS generation, promoted cell apoptosis, and inhibited cell proliferation.2) The antioxidant NAC reversed Cu2+-induced AMPK phosphorylation, ROS generation and cell proliferation inhibition.3) AMPK phosphorylation was also induced by simulated space environment dose- and time-dependently.4) Simulated space environment could induce cell apoptosis in the difference cell passages, which was inhibited by NAC. With the passage number increasing, cell proliferation ability was recovered.5) When simulated space environment -treated cells were recovered in the late passages, the proliferation ability of these cells was still weak if they were treated with oxidative stress (exogenous H2O2).6) After analysing the microRNA sequcecing results and searching the database, has-miR-185, has-miR-23b, has-miR-27a, has-miR-642a, and has-miR-7704 were probably involved in cell proliferation inhibition induced by simulated space environment.These results suggested that copper or simulated space environment induced cell apoptosis, mediated by ROS/AMPK signaling in human B lymphoblasts. Some microRNAs might be involved in simulated space environment-induced AMPK activation.