Copper overload induces apoptosis and impaired proliferation of T cell in zebrafish

Aquat Toxicol. 2023 Dec 19;267:106808. doi: 10.1016/j.aquatox.2023.106808. Online ahead of print.ABSTRACTCopper is an essential biometal for cell development and function, however, unbalanced copper homeostasis in T cell development and the underlying mechanisms are largely unexplored. Here, we use a zebrafish model to investigate the effect of copper overload in T cell development. We show that copper stressed zebrafish larvae exhibit a significant reduction in T cells with increased cell apoptosis and impaired cell proliferation. T cell progenitors, hematopoietic stem and progenitor cells, also exhibit increased cell apoptosis. Copper overload induces production of ROS and the down-regulations of its resistance genes foxos, and ectopic expression of foxo3a, ROS scavenger GSH, could both effectively rescue the reduction of T cells in copper overload larvae. Moreover, foxm1-cytoskeleton axis, parallel to ROS-foxo axis, also mediates the copper overload induced T cell developmental defects. Meanwhile, ROS destroys expression of cytoskeleton rather than of foxm1 in the cells to induce cell apoptosis and the impaired proliferation. The functional integrity of copper transporters cox17 and atp7b are required for copper stress in inducing T cell apoptosis and proliferation impairment. Our findings demonstrate that the down-stream ROS-foxo/cytoskeleton and foxm1-cytoskeleton signaling pathways contribute jointly to copper overload induced T cell apoptosis and proliferation defects,...

Source: Aquatic Toxicology - December 30, 2023 Category: Toxicology Authors: LingYa Li JiaHao Shi WenYe Liu Yi Luo Sheng Gao Jing-Xia Liu Source Type: research