Copper induces apoptotic cell death through reactive oxygen species-triggered oxidative stress in the intertidal copepod Tigriopus japonicus

The copepod, Tigriopus japonicus is an important model for toxicity testing. However, no attempt has been made in analyzing the effect of toxicants at the level of the ROS-mediated signal transduction pathway. To understand copper-induced cytotoxicity at the molecular level, we employed several cellular and biochemical assays after exposure to copper, and found a significant induction of enzyme activities of antioxidant proteins with increased intracellular reactive oxygen species (ROS) as well as an increase of TUNEL-positive cells, but a decrease of BrdU-positive cells. In addition, several important genes such as p38 MAPK, antioxidant-related genes, Hsps, and apoptosis-related genes were significantly modulated by copper exposure. Taken together, we suggest that copper-induced cytotoxicity is mediated by the formation of intracellular ROS and oxidative stress in T. japonicus. Whole body biochemical assays such as TUNEL- and BrdU-assay will provide a better understanding of cellular responses such as apoptosis and cell death upon cytotoxic exposure of copper in T. japonicus.